anno_start	anno_end	anno_text	entity_type	sentence	section
0	33	X-ray Crystallographic Structures	evidence	X-ray Crystallographic Structures of a Trimer, Dodecamer, and Annular Pore Formed by an Aβ17–36 β-Hairpin	TITLE
39	45	Trimer	oligomeric_state	X-ray Crystallographic Structures of a Trimer, Dodecamer, and Annular Pore Formed by an Aβ17–36 β-Hairpin	TITLE
47	56	Dodecamer	oligomeric_state	X-ray Crystallographic Structures of a Trimer, Dodecamer, and Annular Pore Formed by an Aβ17–36 β-Hairpin	TITLE
62	74	Annular Pore	site	X-ray Crystallographic Structures of a Trimer, Dodecamer, and Annular Pore Formed by an Aβ17–36 β-Hairpin	TITLE
88	90	Aβ	protein	X-ray Crystallographic Structures of a Trimer, Dodecamer, and Annular Pore Formed by an Aβ17–36 β-Hairpin	TITLE
90	95	17–36	residue_range	X-ray Crystallographic Structures of a Trimer, Dodecamer, and Annular Pore Formed by an Aβ17–36 β-Hairpin	TITLE
96	105	β-Hairpin	structure_element	X-ray Crystallographic Structures of a Trimer, Dodecamer, and Annular Pore Formed by an Aβ17–36 β-Hairpin	TITLE
16	26	structures	evidence	High-resolution structures of oligomers formed by the β-amyloid peptide Aβ are needed to understand the molecular basis of Alzheimer’s disease and develop therapies.	ABSTRACT
30	39	oligomers	oligomeric_state	High-resolution structures of oligomers formed by the β-amyloid peptide Aβ are needed to understand the molecular basis of Alzheimer’s disease and develop therapies.	ABSTRACT
54	71	β-amyloid peptide	protein	High-resolution structures of oligomers formed by the β-amyloid peptide Aβ are needed to understand the molecular basis of Alzheimer’s disease and develop therapies.	ABSTRACT
72	74	Aβ	protein	High-resolution structures of oligomers formed by the β-amyloid peptide Aβ are needed to understand the molecular basis of Alzheimer’s disease and develop therapies.	ABSTRACT
24	57	X-ray crystallographic structures	evidence	This paper presents the X-ray crystallographic structures of oligomers formed by a 20-residue peptide segment derived from Aβ.	ABSTRACT
61	70	oligomers	oligomeric_state	This paper presents the X-ray crystallographic structures of oligomers formed by a 20-residue peptide segment derived from Aβ.	ABSTRACT
83	109	20-residue peptide segment	residue_range	This paper presents the X-ray crystallographic structures of oligomers formed by a 20-residue peptide segment derived from Aβ.	ABSTRACT
123	125	Aβ	protein	This paper presents the X-ray crystallographic structures of oligomers formed by a 20-residue peptide segment derived from Aβ.	ABSTRACT
38	40	Aβ	protein	The development of a peptide in which Aβ17–36 is stabilized as a β-hairpin is described, and the X-ray crystallographic structures of oligomers it forms are reported.	ABSTRACT
40	45	17–36	residue_range	The development of a peptide in which Aβ17–36 is stabilized as a β-hairpin is described, and the X-ray crystallographic structures of oligomers it forms are reported.	ABSTRACT
65	74	β-hairpin	structure_element	The development of a peptide in which Aβ17–36 is stabilized as a β-hairpin is described, and the X-ray crystallographic structures of oligomers it forms are reported.	ABSTRACT
97	130	X-ray crystallographic structures	evidence	The development of a peptide in which Aβ17–36 is stabilized as a β-hairpin is described, and the X-ray crystallographic structures of oligomers it forms are reported.	ABSTRACT
134	143	oligomers	oligomeric_state	The development of a peptide in which Aβ17–36 is stabilized as a β-hairpin is described, and the X-ray crystallographic structures of oligomers it forms are reported.	ABSTRACT
56	58	Aβ	protein	Two covalent constraints act in tandem to stabilize the Aβ17–36 peptide in a hairpin conformation: a δ-linked ornithine turn connecting positions 17 and 36 to create a macrocycle and an intramolecular disulfide linkage between positions 24 and 29.	ABSTRACT
58	63	17–36	residue_range	Two covalent constraints act in tandem to stabilize the Aβ17–36 peptide in a hairpin conformation: a δ-linked ornithine turn connecting positions 17 and 36 to create a macrocycle and an intramolecular disulfide linkage between positions 24 and 29.	ABSTRACT
77	84	hairpin	structure_element	Two covalent constraints act in tandem to stabilize the Aβ17–36 peptide in a hairpin conformation: a δ-linked ornithine turn connecting positions 17 and 36 to create a macrocycle and an intramolecular disulfide linkage between positions 24 and 29.	ABSTRACT
101	109	δ-linked	protein_state	Two covalent constraints act in tandem to stabilize the Aβ17–36 peptide in a hairpin conformation: a δ-linked ornithine turn connecting positions 17 and 36 to create a macrocycle and an intramolecular disulfide linkage between positions 24 and 29.	ABSTRACT
110	119	ornithine	residue_name	Two covalent constraints act in tandem to stabilize the Aβ17–36 peptide in a hairpin conformation: a δ-linked ornithine turn connecting positions 17 and 36 to create a macrocycle and an intramolecular disulfide linkage between positions 24 and 29.	ABSTRACT
120	124	turn	structure_element	Two covalent constraints act in tandem to stabilize the Aβ17–36 peptide in a hairpin conformation: a δ-linked ornithine turn connecting positions 17 and 36 to create a macrocycle and an intramolecular disulfide linkage between positions 24 and 29.	ABSTRACT
146	148	17	residue_number	Two covalent constraints act in tandem to stabilize the Aβ17–36 peptide in a hairpin conformation: a δ-linked ornithine turn connecting positions 17 and 36 to create a macrocycle and an intramolecular disulfide linkage between positions 24 and 29.	ABSTRACT
153	155	36	residue_number	Two covalent constraints act in tandem to stabilize the Aβ17–36 peptide in a hairpin conformation: a δ-linked ornithine turn connecting positions 17 and 36 to create a macrocycle and an intramolecular disulfide linkage between positions 24 and 29.	ABSTRACT
201	218	disulfide linkage	ptm	Two covalent constraints act in tandem to stabilize the Aβ17–36 peptide in a hairpin conformation: a δ-linked ornithine turn connecting positions 17 and 36 to create a macrocycle and an intramolecular disulfide linkage between positions 24 and 29.	ABSTRACT
237	239	24	residue_number	Two covalent constraints act in tandem to stabilize the Aβ17–36 peptide in a hairpin conformation: a δ-linked ornithine turn connecting positions 17 and 36 to create a macrocycle and an intramolecular disulfide linkage between positions 24 and 29.	ABSTRACT
244	246	29	residue_number	Two covalent constraints act in tandem to stabilize the Aβ17–36 peptide in a hairpin conformation: a δ-linked ornithine turn connecting positions 17 and 36 to create a macrocycle and an intramolecular disulfide linkage between positions 24 and 29.	ABSTRACT
30	32	33	residue_number	An N-methyl group at position 33 blocks uncontrolled aggregation.	ABSTRACT
12	32	readily crystallizes	evidence	The peptide readily crystallizes as a folded β-hairpin, which assembles hierarchically in the crystal lattice.	ABSTRACT
38	44	folded	protein_state	The peptide readily crystallizes as a folded β-hairpin, which assembles hierarchically in the crystal lattice.	ABSTRACT
45	54	β-hairpin	structure_element	The peptide readily crystallizes as a folded β-hairpin, which assembles hierarchically in the crystal lattice.	ABSTRACT
94	109	crystal lattice	evidence	The peptide readily crystallizes as a folded β-hairpin, which assembles hierarchically in the crystal lattice.	ABSTRACT
6	15	β-hairpin	structure_element	Three β-hairpin monomers assemble to form a triangular trimer, four trimers assemble in a tetrahedral arrangement to form a dodecamer, and five dodecamers pack together to form an annular pore.	ABSTRACT
16	24	monomers	oligomeric_state	Three β-hairpin monomers assemble to form a triangular trimer, four trimers assemble in a tetrahedral arrangement to form a dodecamer, and five dodecamers pack together to form an annular pore.	ABSTRACT
44	54	triangular	protein_state	Three β-hairpin monomers assemble to form a triangular trimer, four trimers assemble in a tetrahedral arrangement to form a dodecamer, and five dodecamers pack together to form an annular pore.	ABSTRACT
55	61	trimer	oligomeric_state	Three β-hairpin monomers assemble to form a triangular trimer, four trimers assemble in a tetrahedral arrangement to form a dodecamer, and five dodecamers pack together to form an annular pore.	ABSTRACT
68	75	trimers	oligomeric_state	Three β-hairpin monomers assemble to form a triangular trimer, four trimers assemble in a tetrahedral arrangement to form a dodecamer, and five dodecamers pack together to form an annular pore.	ABSTRACT
124	133	dodecamer	oligomeric_state	Three β-hairpin monomers assemble to form a triangular trimer, four trimers assemble in a tetrahedral arrangement to form a dodecamer, and five dodecamers pack together to form an annular pore.	ABSTRACT
144	154	dodecamers	oligomeric_state	Three β-hairpin monomers assemble to form a triangular trimer, four trimers assemble in a tetrahedral arrangement to form a dodecamer, and five dodecamers pack together to form an annular pore.	ABSTRACT
180	192	annular pore	site	Three β-hairpin monomers assemble to form a triangular trimer, four trimers assemble in a tetrahedral arrangement to form a dodecamer, and five dodecamers pack together to form an annular pore.	ABSTRACT
54	65	full-length	protein_state	This hierarchical assembly provides a model, in which full-length Aβ transitions from an unfolded monomer to a folded β-hairpin, which assembles to form oligomers that further pack to form an annular pore.	ABSTRACT
66	68	Aβ	protein	This hierarchical assembly provides a model, in which full-length Aβ transitions from an unfolded monomer to a folded β-hairpin, which assembles to form oligomers that further pack to form an annular pore.	ABSTRACT
89	97	unfolded	protein_state	This hierarchical assembly provides a model, in which full-length Aβ transitions from an unfolded monomer to a folded β-hairpin, which assembles to form oligomers that further pack to form an annular pore.	ABSTRACT
98	105	monomer	oligomeric_state	This hierarchical assembly provides a model, in which full-length Aβ transitions from an unfolded monomer to a folded β-hairpin, which assembles to form oligomers that further pack to form an annular pore.	ABSTRACT
111	117	folded	protein_state	This hierarchical assembly provides a model, in which full-length Aβ transitions from an unfolded monomer to a folded β-hairpin, which assembles to form oligomers that further pack to form an annular pore.	ABSTRACT
118	127	β-hairpin	structure_element	This hierarchical assembly provides a model, in which full-length Aβ transitions from an unfolded monomer to a folded β-hairpin, which assembles to form oligomers that further pack to form an annular pore.	ABSTRACT
153	162	oligomers	oligomeric_state	This hierarchical assembly provides a model, in which full-length Aβ transitions from an unfolded monomer to a folded β-hairpin, which assembles to form oligomers that further pack to form an annular pore.	ABSTRACT
192	204	annular pore	site	This hierarchical assembly provides a model, in which full-length Aβ transitions from an unfolded monomer to a folded β-hairpin, which assembles to form oligomers that further pack to form an annular pore.	ABSTRACT
16	26	structures	evidence	High-resolution structures of oligomers formed by the β-amyloid peptide Aβ are desperately needed to understand the molecular basis of Alzheimer’s disease and ultimately develop preventions or treatments.	INTRO
30	39	oligomers	oligomeric_state	High-resolution structures of oligomers formed by the β-amyloid peptide Aβ are desperately needed to understand the molecular basis of Alzheimer’s disease and ultimately develop preventions or treatments.	INTRO
54	71	β-amyloid peptide	protein	High-resolution structures of oligomers formed by the β-amyloid peptide Aβ are desperately needed to understand the molecular basis of Alzheimer’s disease and ultimately develop preventions or treatments.	INTRO
72	74	Aβ	protein	High-resolution structures of oligomers formed by the β-amyloid peptide Aβ are desperately needed to understand the molecular basis of Alzheimer’s disease and ultimately develop preventions or treatments.	INTRO
24	33	monomeric	oligomeric_state	In Alzheimer’s disease, monomeric Aβ aggregates to form soluble low molecular weight oligomers, such as dimers, trimers, tetramers, hexamers, nonamers, and dodecamers, as well as high molecular weight aggregates, such as annular protofibrils.	INTRO
34	36	Aβ	protein	In Alzheimer’s disease, monomeric Aβ aggregates to form soluble low molecular weight oligomers, such as dimers, trimers, tetramers, hexamers, nonamers, and dodecamers, as well as high molecular weight aggregates, such as annular protofibrils.	INTRO
85	94	oligomers	oligomeric_state	In Alzheimer’s disease, monomeric Aβ aggregates to form soluble low molecular weight oligomers, such as dimers, trimers, tetramers, hexamers, nonamers, and dodecamers, as well as high molecular weight aggregates, such as annular protofibrils.	INTRO
104	110	dimers	oligomeric_state	In Alzheimer’s disease, monomeric Aβ aggregates to form soluble low molecular weight oligomers, such as dimers, trimers, tetramers, hexamers, nonamers, and dodecamers, as well as high molecular weight aggregates, such as annular protofibrils.	INTRO
112	119	trimers	oligomeric_state	In Alzheimer’s disease, monomeric Aβ aggregates to form soluble low molecular weight oligomers, such as dimers, trimers, tetramers, hexamers, nonamers, and dodecamers, as well as high molecular weight aggregates, such as annular protofibrils.	INTRO
121	130	tetramers	oligomeric_state	In Alzheimer’s disease, monomeric Aβ aggregates to form soluble low molecular weight oligomers, such as dimers, trimers, tetramers, hexamers, nonamers, and dodecamers, as well as high molecular weight aggregates, such as annular protofibrils.	INTRO
132	140	hexamers	oligomeric_state	In Alzheimer’s disease, monomeric Aβ aggregates to form soluble low molecular weight oligomers, such as dimers, trimers, tetramers, hexamers, nonamers, and dodecamers, as well as high molecular weight aggregates, such as annular protofibrils.	INTRO
142	150	nonamers	oligomeric_state	In Alzheimer’s disease, monomeric Aβ aggregates to form soluble low molecular weight oligomers, such as dimers, trimers, tetramers, hexamers, nonamers, and dodecamers, as well as high molecular weight aggregates, such as annular protofibrils.	INTRO
156	166	dodecamers	oligomeric_state	In Alzheimer’s disease, monomeric Aβ aggregates to form soluble low molecular weight oligomers, such as dimers, trimers, tetramers, hexamers, nonamers, and dodecamers, as well as high molecular weight aggregates, such as annular protofibrils.	INTRO
221	241	annular protofibrils	complex_assembly	In Alzheimer’s disease, monomeric Aβ aggregates to form soluble low molecular weight oligomers, such as dimers, trimers, tetramers, hexamers, nonamers, and dodecamers, as well as high molecular weight aggregates, such as annular protofibrils.	INTRO
38	40	Aβ	protein	Over the last two decades the role of Aβ oligomers in the pathophysiology of Alzheimer’s disease has begun to unfold.	INTRO
41	50	oligomers	oligomeric_state	Over the last two decades the role of Aβ oligomers in the pathophysiology of Alzheimer’s disease has begun to unfold.	INTRO
0	5	Mouse	taxonomy_domain	Mouse models for Alzheimer’s disease have helped shape our current understanding about the Aβ oligomerization that precedes neurodegeneration.	INTRO
91	93	Aβ	protein	Mouse models for Alzheimer’s disease have helped shape our current understanding about the Aβ oligomerization that precedes neurodegeneration.	INTRO
0	2	Aβ	protein	Aβ isolated from the brains of young plaque-free Tg2576 mice forms a mixture of low molecular weight oligomers.	INTRO
56	60	mice	taxonomy_domain	Aβ isolated from the brains of young plaque-free Tg2576 mice forms a mixture of low molecular weight oligomers.	INTRO
101	110	oligomers	oligomeric_state	Aβ isolated from the brains of young plaque-free Tg2576 mice forms a mixture of low molecular weight oligomers.	INTRO
17	25	oligomer	oligomeric_state	A 56 kDa soluble oligomer identified by SDS-PAGE was found to be especially important within this mixture.	INTRO
40	48	SDS-PAGE	experimental_method	A 56 kDa soluble oligomer identified by SDS-PAGE was found to be especially important within this mixture.	INTRO
5	13	oligomer	oligomeric_state	This oligomer was termed Aβ*56 and appears to be a dodecamer of Aβ.	INTRO
25	30	Aβ*56	complex_assembly	This oligomer was termed Aβ*56 and appears to be a dodecamer of Aβ.	INTRO
51	60	dodecamer	oligomeric_state	This oligomer was termed Aβ*56 and appears to be a dodecamer of Aβ.	INTRO
64	66	Aβ	protein	This oligomer was termed Aβ*56 and appears to be a dodecamer of Aβ.	INTRO
9	14	Aβ*56	complex_assembly	Purified Aβ*56 injected intercranially into healthy rats was found to impair memory, providing evidence that this Aβ oligomer may cause memory loss in Alzheimer’s disease.	INTRO
15	38	injected intercranially	experimental_method	Purified Aβ*56 injected intercranially into healthy rats was found to impair memory, providing evidence that this Aβ oligomer may cause memory loss in Alzheimer’s disease.	INTRO
52	56	rats	taxonomy_domain	Purified Aβ*56 injected intercranially into healthy rats was found to impair memory, providing evidence that this Aβ oligomer may cause memory loss in Alzheimer’s disease.	INTRO
114	116	Aβ	protein	Purified Aβ*56 injected intercranially into healthy rats was found to impair memory, providing evidence that this Aβ oligomer may cause memory loss in Alzheimer’s disease.	INTRO
117	125	oligomer	oligomeric_state	Purified Aβ*56 injected intercranially into healthy rats was found to impair memory, providing evidence that this Aβ oligomer may cause memory loss in Alzheimer’s disease.	INTRO
8	17	oligomers	oligomeric_state	Smaller oligomers with molecular weights consistent with trimers, hexamers, and nonamers were also identified within the mixture of low molecular weight oligomers.	INTRO
57	64	trimers	oligomeric_state	Smaller oligomers with molecular weights consistent with trimers, hexamers, and nonamers were also identified within the mixture of low molecular weight oligomers.	INTRO
66	74	hexamers	oligomeric_state	Smaller oligomers with molecular weights consistent with trimers, hexamers, and nonamers were also identified within the mixture of low molecular weight oligomers.	INTRO
80	88	nonamers	oligomeric_state	Smaller oligomers with molecular weights consistent with trimers, hexamers, and nonamers were also identified within the mixture of low molecular weight oligomers.	INTRO
153	162	oligomers	oligomeric_state	Smaller oligomers with molecular weights consistent with trimers, hexamers, and nonamers were also identified within the mixture of low molecular weight oligomers.	INTRO
49	58	oligomers	oligomeric_state	Treatment of the mixture of low molecular weight oligomers with hexafluoroisopropanol resulted in the dissociation of the putative dodecamers, nonamers, and hexamers into trimers and monomers, suggesting that trimers may be the building block of the dodecamers, nonamers, and hexamers.	INTRO
64	85	hexafluoroisopropanol	chemical	Treatment of the mixture of low molecular weight oligomers with hexafluoroisopropanol resulted in the dissociation of the putative dodecamers, nonamers, and hexamers into trimers and monomers, suggesting that trimers may be the building block of the dodecamers, nonamers, and hexamers.	INTRO
131	141	dodecamers	oligomeric_state	Treatment of the mixture of low molecular weight oligomers with hexafluoroisopropanol resulted in the dissociation of the putative dodecamers, nonamers, and hexamers into trimers and monomers, suggesting that trimers may be the building block of the dodecamers, nonamers, and hexamers.	INTRO
143	151	nonamers	oligomeric_state	Treatment of the mixture of low molecular weight oligomers with hexafluoroisopropanol resulted in the dissociation of the putative dodecamers, nonamers, and hexamers into trimers and monomers, suggesting that trimers may be the building block of the dodecamers, nonamers, and hexamers.	INTRO
157	165	hexamers	oligomeric_state	Treatment of the mixture of low molecular weight oligomers with hexafluoroisopropanol resulted in the dissociation of the putative dodecamers, nonamers, and hexamers into trimers and monomers, suggesting that trimers may be the building block of the dodecamers, nonamers, and hexamers.	INTRO
171	178	trimers	oligomeric_state	Treatment of the mixture of low molecular weight oligomers with hexafluoroisopropanol resulted in the dissociation of the putative dodecamers, nonamers, and hexamers into trimers and monomers, suggesting that trimers may be the building block of the dodecamers, nonamers, and hexamers.	INTRO
183	191	monomers	oligomeric_state	Treatment of the mixture of low molecular weight oligomers with hexafluoroisopropanol resulted in the dissociation of the putative dodecamers, nonamers, and hexamers into trimers and monomers, suggesting that trimers may be the building block of the dodecamers, nonamers, and hexamers.	INTRO
209	216	trimers	oligomeric_state	Treatment of the mixture of low molecular weight oligomers with hexafluoroisopropanol resulted in the dissociation of the putative dodecamers, nonamers, and hexamers into trimers and monomers, suggesting that trimers may be the building block of the dodecamers, nonamers, and hexamers.	INTRO
250	260	dodecamers	oligomeric_state	Treatment of the mixture of low molecular weight oligomers with hexafluoroisopropanol resulted in the dissociation of the putative dodecamers, nonamers, and hexamers into trimers and monomers, suggesting that trimers may be the building block of the dodecamers, nonamers, and hexamers.	INTRO
262	270	nonamers	oligomeric_state	Treatment of the mixture of low molecular weight oligomers with hexafluoroisopropanol resulted in the dissociation of the putative dodecamers, nonamers, and hexamers into trimers and monomers, suggesting that trimers may be the building block of the dodecamers, nonamers, and hexamers.	INTRO
276	284	hexamers	oligomeric_state	Treatment of the mixture of low molecular weight oligomers with hexafluoroisopropanol resulted in the dissociation of the putative dodecamers, nonamers, and hexamers into trimers and monomers, suggesting that trimers may be the building block of the dodecamers, nonamers, and hexamers.	INTRO
10	12	Aβ	protein	Recently, Aβ trimers and Aβ*56 were identified in the brains of cognitively normal humans and were found to increase with age.	INTRO
13	20	trimers	oligomeric_state	Recently, Aβ trimers and Aβ*56 were identified in the brains of cognitively normal humans and were found to increase with age.	INTRO
25	30	Aβ*56	complex_assembly	Recently, Aβ trimers and Aβ*56 were identified in the brains of cognitively normal humans and were found to increase with age.	INTRO
83	89	humans	species	Recently, Aβ trimers and Aβ*56 were identified in the brains of cognitively normal humans and were found to increase with age.	INTRO
16	25	oligomers	oligomeric_state	A type of large oligomers called annular protofibrils (APFs) have also been observed in the brains of transgenic mice and isolated from the brains of Alzheimer’s patients.	INTRO
33	53	annular protofibrils	complex_assembly	A type of large oligomers called annular protofibrils (APFs) have also been observed in the brains of transgenic mice and isolated from the brains of Alzheimer’s patients.	INTRO
55	59	APFs	complex_assembly	A type of large oligomers called annular protofibrils (APFs) have also been observed in the brains of transgenic mice and isolated from the brains of Alzheimer’s patients.	INTRO
113	117	mice	taxonomy_domain	A type of large oligomers called annular protofibrils (APFs) have also been observed in the brains of transgenic mice and isolated from the brains of Alzheimer’s patients.	INTRO
0	4	APFs	complex_assembly	APFs were first discovered in vitro using chemically synthesized Aβ that aggregated into porelike structures that could be observed by atomic force microscopy (AFM) and transmission electron microscopy (TEM).	INTRO
42	64	chemically synthesized	protein_state	APFs were first discovered in vitro using chemically synthesized Aβ that aggregated into porelike structures that could be observed by atomic force microscopy (AFM) and transmission electron microscopy (TEM).	INTRO
65	67	Aβ	protein	APFs were first discovered in vitro using chemically synthesized Aβ that aggregated into porelike structures that could be observed by atomic force microscopy (AFM) and transmission electron microscopy (TEM).	INTRO
89	108	porelike structures	structure_element	APFs were first discovered in vitro using chemically synthesized Aβ that aggregated into porelike structures that could be observed by atomic force microscopy (AFM) and transmission electron microscopy (TEM).	INTRO
135	158	atomic force microscopy	experimental_method	APFs were first discovered in vitro using chemically synthesized Aβ that aggregated into porelike structures that could be observed by atomic force microscopy (AFM) and transmission electron microscopy (TEM).	INTRO
160	163	AFM	experimental_method	APFs were first discovered in vitro using chemically synthesized Aβ that aggregated into porelike structures that could be observed by atomic force microscopy (AFM) and transmission electron microscopy (TEM).	INTRO
169	201	transmission electron microscopy	experimental_method	APFs were first discovered in vitro using chemically synthesized Aβ that aggregated into porelike structures that could be observed by atomic force microscopy (AFM) and transmission electron microscopy (TEM).	INTRO
203	206	TEM	experimental_method	APFs were first discovered in vitro using chemically synthesized Aβ that aggregated into porelike structures that could be observed by atomic force microscopy (AFM) and transmission electron microscopy (TEM).	INTRO
13	17	APFs	complex_assembly	The sizes of APFs prepared in vitro vary among different studies.	INTRO
24	28	APFs	complex_assembly	Lashuel et al. observed APFs with an outer diameter that ranged from 7–10 nm and an inner diameter that ranged from 1.5–2 nm, consistent with molecular weights of 150–250 kDa.	INTRO
22	26	APFs	complex_assembly	Quist et al. observed APFs with an outer diameter of 16 nm embedded in a lipid bilayer.	INTRO
22	26	APFs	complex_assembly	Kayed et al. observed APFs with an outer diameter that ranged from 8–25 nm, which were composed of small spherical Aβ oligomers, 3–5 nm in diameter.	INTRO
99	114	small spherical	protein_state	Kayed et al. observed APFs with an outer diameter that ranged from 8–25 nm, which were composed of small spherical Aβ oligomers, 3–5 nm in diameter.	INTRO
115	117	Aβ	protein	Kayed et al. observed APFs with an outer diameter that ranged from 8–25 nm, which were composed of small spherical Aβ oligomers, 3–5 nm in diameter.	INTRO
118	127	oligomers	oligomeric_state	Kayed et al. observed APFs with an outer diameter that ranged from 8–25 nm, which were composed of small spherical Aβ oligomers, 3–5 nm in diameter.	INTRO
13	17	APFs	complex_assembly	Although the APFs in these studies differ in size, they share a similar annular morphology and appear to be composed of smaller oligomers.	INTRO
128	137	oligomers	oligomeric_state	Although the APFs in these studies differ in size, they share a similar annular morphology and appear to be composed of smaller oligomers.	INTRO
0	4	APFs	complex_assembly	APFs have also been observed in the brains of APP23 transgenic mice by immunofluorescence with an anti-APF antibody and were found to accumulate in neuronal processes and synapses.	INTRO
63	67	mice	taxonomy_domain	APFs have also been observed in the brains of APP23 transgenic mice by immunofluorescence with an anti-APF antibody and were found to accumulate in neuronal processes and synapses.	INTRO
71	89	immunofluorescence	experimental_method	APFs have also been observed in the brains of APP23 transgenic mice by immunofluorescence with an anti-APF antibody and were found to accumulate in neuronal processes and synapses.	INTRO
103	106	APF	complex_assembly	APFs have also been observed in the brains of APP23 transgenic mice by immunofluorescence with an anti-APF antibody and were found to accumulate in neuronal processes and synapses.	INTRO
23	27	APFs	complex_assembly	In a subsequent study, APFs were isolated from the brains of Alzheimer’s patients by immunoprecipitation with an anti-APF antibody.	INTRO
85	104	immunoprecipitation	experimental_method	In a subsequent study, APFs were isolated from the brains of Alzheimer’s patients by immunoprecipitation with an anti-APF antibody.	INTRO
118	121	APF	complex_assembly	In a subsequent study, APFs were isolated from the brains of Alzheimer’s patients by immunoprecipitation with an anti-APF antibody.	INTRO
6	10	APFs	complex_assembly	These APFs had an outer diameter that ranged from 11–14 nm and an inner diameter that ranged from 2.5–4 nm.	INTRO
0	6	Dimers	oligomeric_state	Dimers of Aβ have also been isolated from the brains of Alzheimer’s patients.− Aβ dimers inhibit long-term potentiation in mice and promote hyperphosphorylation of the microtubule-associated protein tau, leading to neuritic damage.	INTRO
10	12	Aβ	protein	Dimers of Aβ have also been isolated from the brains of Alzheimer’s patients.− Aβ dimers inhibit long-term potentiation in mice and promote hyperphosphorylation of the microtubule-associated protein tau, leading to neuritic damage.	INTRO
79	81	Aβ	protein	Dimers of Aβ have also been isolated from the brains of Alzheimer’s patients.− Aβ dimers inhibit long-term potentiation in mice and promote hyperphosphorylation of the microtubule-associated protein tau, leading to neuritic damage.	INTRO
82	88	dimers	oligomeric_state	Dimers of Aβ have also been isolated from the brains of Alzheimer’s patients.− Aβ dimers inhibit long-term potentiation in mice and promote hyperphosphorylation of the microtubule-associated protein tau, leading to neuritic damage.	INTRO
123	127	mice	taxonomy_domain	Dimers of Aβ have also been isolated from the brains of Alzheimer’s patients.− Aβ dimers inhibit long-term potentiation in mice and promote hyperphosphorylation of the microtubule-associated protein tau, leading to neuritic damage.	INTRO
140	160	hyperphosphorylation	ptm	Dimers of Aβ have also been isolated from the brains of Alzheimer’s patients.− Aβ dimers inhibit long-term potentiation in mice and promote hyperphosphorylation of the microtubule-associated protein tau, leading to neuritic damage.	INTRO
168	202	microtubule-associated protein tau	protein	Dimers of Aβ have also been isolated from the brains of Alzheimer’s patients.− Aβ dimers inhibit long-term potentiation in mice and promote hyperphosphorylation of the microtubule-associated protein tau, leading to neuritic damage.	INTRO
0	2	Aβ	protein	Aβ dimers have only been isolated from human or transgenic mouse brains that contain the pathognomonic fibrillar Aβ plaques associated with Alzheimer’s disease.	INTRO
3	9	dimers	oligomeric_state	Aβ dimers have only been isolated from human or transgenic mouse brains that contain the pathognomonic fibrillar Aβ plaques associated with Alzheimer’s disease.	INTRO
39	44	human	species	Aβ dimers have only been isolated from human or transgenic mouse brains that contain the pathognomonic fibrillar Aβ plaques associated with Alzheimer’s disease.	INTRO
59	64	mouse	taxonomy_domain	Aβ dimers have only been isolated from human or transgenic mouse brains that contain the pathognomonic fibrillar Aβ plaques associated with Alzheimer’s disease.	INTRO
103	112	fibrillar	protein_state	Aβ dimers have only been isolated from human or transgenic mouse brains that contain the pathognomonic fibrillar Aβ plaques associated with Alzheimer’s disease.	INTRO
113	115	Aβ	protein	Aβ dimers have only been isolated from human or transgenic mouse brains that contain the pathognomonic fibrillar Aβ plaques associated with Alzheimer’s disease.	INTRO
36	38	Aβ	protein	Furthermore, the endogenous rise of Aβ dimers in the brains of Tg2576 and J20 transgenic mice coincides with the deposition of Aβ plaques.	INTRO
39	45	dimers	oligomeric_state	Furthermore, the endogenous rise of Aβ dimers in the brains of Tg2576 and J20 transgenic mice coincides with the deposition of Aβ plaques.	INTRO
89	93	mice	taxonomy_domain	Furthermore, the endogenous rise of Aβ dimers in the brains of Tg2576 and J20 transgenic mice coincides with the deposition of Aβ plaques.	INTRO
127	129	Aβ	protein	Furthermore, the endogenous rise of Aβ dimers in the brains of Tg2576 and J20 transgenic mice coincides with the deposition of Aβ plaques.	INTRO
36	38	Aβ	protein	These observations suggest that the Aβ trimers, hexamers, dodecamers, and related assemblies may be associated with presymptomatic neurodegeneration, while Aβ dimers are more closely associated with fibril formation and plaque deposition during symptomatic Alzheimer’s disease.−	INTRO
39	46	trimers	oligomeric_state	These observations suggest that the Aβ trimers, hexamers, dodecamers, and related assemblies may be associated with presymptomatic neurodegeneration, while Aβ dimers are more closely associated with fibril formation and plaque deposition during symptomatic Alzheimer’s disease.−	INTRO
48	56	hexamers	oligomeric_state	These observations suggest that the Aβ trimers, hexamers, dodecamers, and related assemblies may be associated with presymptomatic neurodegeneration, while Aβ dimers are more closely associated with fibril formation and plaque deposition during symptomatic Alzheimer’s disease.−	INTRO
58	68	dodecamers	oligomeric_state	These observations suggest that the Aβ trimers, hexamers, dodecamers, and related assemblies may be associated with presymptomatic neurodegeneration, while Aβ dimers are more closely associated with fibril formation and plaque deposition during symptomatic Alzheimer’s disease.−	INTRO
156	158	Aβ	protein	These observations suggest that the Aβ trimers, hexamers, dodecamers, and related assemblies may be associated with presymptomatic neurodegeneration, while Aβ dimers are more closely associated with fibril formation and plaque deposition during symptomatic Alzheimer’s disease.−	INTRO
159	165	dimers	oligomeric_state	These observations suggest that the Aβ trimers, hexamers, dodecamers, and related assemblies may be associated with presymptomatic neurodegeneration, while Aβ dimers are more closely associated with fibril formation and plaque deposition during symptomatic Alzheimer’s disease.−	INTRO
45	47	Aβ	protein	The approach of isolating and characterizing Aβ oligomers has not provided any high-resolution structures of Aβ oligomers.	INTRO
48	57	oligomers	oligomeric_state	The approach of isolating and characterizing Aβ oligomers has not provided any high-resolution structures of Aβ oligomers.	INTRO
95	105	structures	evidence	The approach of isolating and characterizing Aβ oligomers has not provided any high-resolution structures of Aβ oligomers.	INTRO
109	111	Aβ	protein	The approach of isolating and characterizing Aβ oligomers has not provided any high-resolution structures of Aβ oligomers.	INTRO
112	121	oligomers	oligomeric_state	The approach of isolating and characterizing Aβ oligomers has not provided any high-resolution structures of Aβ oligomers.	INTRO
19	27	SDS-PAGE	experimental_method	Techniques such as SDS-PAGE, TEM, and AFM have only provided information about the molecular weights, sizes, morphologies, and stoichiometry of Aβ oligomers.	INTRO
29	32	TEM	experimental_method	Techniques such as SDS-PAGE, TEM, and AFM have only provided information about the molecular weights, sizes, morphologies, and stoichiometry of Aβ oligomers.	INTRO
38	41	AFM	experimental_method	Techniques such as SDS-PAGE, TEM, and AFM have only provided information about the molecular weights, sizes, morphologies, and stoichiometry of Aβ oligomers.	INTRO
144	146	Aβ	protein	Techniques such as SDS-PAGE, TEM, and AFM have only provided information about the molecular weights, sizes, morphologies, and stoichiometry of Aβ oligomers.	INTRO
147	156	oligomers	oligomeric_state	Techniques such as SDS-PAGE, TEM, and AFM have only provided information about the molecular weights, sizes, morphologies, and stoichiometry of Aβ oligomers.	INTRO
16	34	structural studies	experimental_method	High-resolution structural studies of Aβ have primarily focused on Aβ fibrils and Aβ monomers.	INTRO
38	40	Aβ	protein	High-resolution structural studies of Aβ have primarily focused on Aβ fibrils and Aβ monomers.	INTRO
67	69	Aβ	protein	High-resolution structural studies of Aβ have primarily focused on Aβ fibrils and Aβ monomers.	INTRO
70	77	fibrils	oligomeric_state	High-resolution structural studies of Aβ have primarily focused on Aβ fibrils and Aβ monomers.	INTRO
82	84	Aβ	protein	High-resolution structural studies of Aβ have primarily focused on Aβ fibrils and Aβ monomers.	INTRO
85	93	monomers	oligomeric_state	High-resolution structural studies of Aβ have primarily focused on Aβ fibrils and Aβ monomers.	INTRO
0	28	Solid-state NMR spectroscopy	experimental_method	Solid-state NMR spectroscopy studies of Aβ fibrils revealed that Aβ fibrils are generally composed of extended networks of in-register parallel β-sheets.− X-ray crystallographic studies using fragments of Aβ have provided additional information about how Aβ fibrils pack.	INTRO
40	42	Aβ	protein	Solid-state NMR spectroscopy studies of Aβ fibrils revealed that Aβ fibrils are generally composed of extended networks of in-register parallel β-sheets.− X-ray crystallographic studies using fragments of Aβ have provided additional information about how Aβ fibrils pack.	INTRO
43	50	fibrils	oligomeric_state	Solid-state NMR spectroscopy studies of Aβ fibrils revealed that Aβ fibrils are generally composed of extended networks of in-register parallel β-sheets.− X-ray crystallographic studies using fragments of Aβ have provided additional information about how Aβ fibrils pack.	INTRO
65	67	Aβ	protein	Solid-state NMR spectroscopy studies of Aβ fibrils revealed that Aβ fibrils are generally composed of extended networks of in-register parallel β-sheets.− X-ray crystallographic studies using fragments of Aβ have provided additional information about how Aβ fibrils pack.	INTRO
68	75	fibrils	oligomeric_state	Solid-state NMR spectroscopy studies of Aβ fibrils revealed that Aβ fibrils are generally composed of extended networks of in-register parallel β-sheets.− X-ray crystallographic studies using fragments of Aβ have provided additional information about how Aβ fibrils pack.	INTRO
123	152	in-register parallel β-sheets	structure_element	Solid-state NMR spectroscopy studies of Aβ fibrils revealed that Aβ fibrils are generally composed of extended networks of in-register parallel β-sheets.− X-ray crystallographic studies using fragments of Aβ have provided additional information about how Aβ fibrils pack.	INTRO
155	185	X-ray crystallographic studies	experimental_method	Solid-state NMR spectroscopy studies of Aβ fibrils revealed that Aβ fibrils are generally composed of extended networks of in-register parallel β-sheets.− X-ray crystallographic studies using fragments of Aβ have provided additional information about how Aβ fibrils pack.	INTRO
205	207	Aβ	protein	Solid-state NMR spectroscopy studies of Aβ fibrils revealed that Aβ fibrils are generally composed of extended networks of in-register parallel β-sheets.− X-ray crystallographic studies using fragments of Aβ have provided additional information about how Aβ fibrils pack.	INTRO
255	257	Aβ	protein	Solid-state NMR spectroscopy studies of Aβ fibrils revealed that Aβ fibrils are generally composed of extended networks of in-register parallel β-sheets.− X-ray crystallographic studies using fragments of Aβ have provided additional information about how Aβ fibrils pack.	INTRO
258	265	fibrils	oligomeric_state	Solid-state NMR spectroscopy studies of Aβ fibrils revealed that Aβ fibrils are generally composed of extended networks of in-register parallel β-sheets.− X-ray crystallographic studies using fragments of Aβ have provided additional information about how Aβ fibrils pack.	INTRO
0	18	Solution-phase NMR	experimental_method	Solution-phase NMR and solid-state NMR have been used to study the structures of the Aβ monomers within oligomeric assemblies.− A major finding from these studies is that oligomeric assemblies of Aβ are primarily composed of antiparallel β-sheets.	INTRO
23	38	solid-state NMR	experimental_method	Solution-phase NMR and solid-state NMR have been used to study the structures of the Aβ monomers within oligomeric assemblies.− A major finding from these studies is that oligomeric assemblies of Aβ are primarily composed of antiparallel β-sheets.	INTRO
67	77	structures	evidence	Solution-phase NMR and solid-state NMR have been used to study the structures of the Aβ monomers within oligomeric assemblies.− A major finding from these studies is that oligomeric assemblies of Aβ are primarily composed of antiparallel β-sheets.	INTRO
85	87	Aβ	protein	Solution-phase NMR and solid-state NMR have been used to study the structures of the Aβ monomers within oligomeric assemblies.− A major finding from these studies is that oligomeric assemblies of Aβ are primarily composed of antiparallel β-sheets.	INTRO
88	96	monomers	oligomeric_state	Solution-phase NMR and solid-state NMR have been used to study the structures of the Aβ monomers within oligomeric assemblies.− A major finding from these studies is that oligomeric assemblies of Aβ are primarily composed of antiparallel β-sheets.	INTRO
196	198	Aβ	protein	Solution-phase NMR and solid-state NMR have been used to study the structures of the Aβ monomers within oligomeric assemblies.− A major finding from these studies is that oligomeric assemblies of Aβ are primarily composed of antiparallel β-sheets.	INTRO
225	246	antiparallel β-sheets	structure_element	Solution-phase NMR and solid-state NMR have been used to study the structures of the Aβ monomers within oligomeric assemblies.− A major finding from these studies is that oligomeric assemblies of Aβ are primarily composed of antiparallel β-sheets.	INTRO
40	47	monomer	oligomeric_state	Many of these studies have reported the monomer subunit as adopting a β-hairpin conformation, in which the hydrophobic central and C-terminal regions form an antiparallel β-sheet.	INTRO
48	55	subunit	structure_element	Many of these studies have reported the monomer subunit as adopting a β-hairpin conformation, in which the hydrophobic central and C-terminal regions form an antiparallel β-sheet.	INTRO
70	79	β-hairpin	structure_element	Many of these studies have reported the monomer subunit as adopting a β-hairpin conformation, in which the hydrophobic central and C-terminal regions form an antiparallel β-sheet.	INTRO
119	126	central	structure_element	Many of these studies have reported the monomer subunit as adopting a β-hairpin conformation, in which the hydrophobic central and C-terminal regions form an antiparallel β-sheet.	INTRO
131	149	C-terminal regions	structure_element	Many of these studies have reported the monomer subunit as adopting a β-hairpin conformation, in which the hydrophobic central and C-terminal regions form an antiparallel β-sheet.	INTRO
158	178	antiparallel β-sheet	structure_element	Many of these studies have reported the monomer subunit as adopting a β-hairpin conformation, in which the hydrophobic central and C-terminal regions form an antiparallel β-sheet.	INTRO
35	38	NMR	experimental_method	In 2008, Hoyer et al. reported the NMR structure of an Aβ monomer bound to an artificial binding protein called an affibody (PDB 2OTK).	INTRO
39	48	structure	evidence	In 2008, Hoyer et al. reported the NMR structure of an Aβ monomer bound to an artificial binding protein called an affibody (PDB 2OTK).	INTRO
55	57	Aβ	protein	In 2008, Hoyer et al. reported the NMR structure of an Aβ monomer bound to an artificial binding protein called an affibody (PDB 2OTK).	INTRO
58	65	monomer	oligomeric_state	In 2008, Hoyer et al. reported the NMR structure of an Aβ monomer bound to an artificial binding protein called an affibody (PDB 2OTK).	INTRO
66	74	bound to	protein_state	In 2008, Hoyer et al. reported the NMR structure of an Aβ monomer bound to an artificial binding protein called an affibody (PDB 2OTK).	INTRO
78	104	artificial binding protein	chemical	In 2008, Hoyer et al. reported the NMR structure of an Aβ monomer bound to an artificial binding protein called an affibody (PDB 2OTK).	INTRO
115	123	affibody	chemical	In 2008, Hoyer et al. reported the NMR structure of an Aβ monomer bound to an artificial binding protein called an affibody (PDB 2OTK).	INTRO
4	13	structure	evidence	The structure revealed that monomeric Aβ forms a β-hairpin when bound to the affibody.	INTRO
28	37	monomeric	oligomeric_state	The structure revealed that monomeric Aβ forms a β-hairpin when bound to the affibody.	INTRO
38	40	Aβ	protein	The structure revealed that monomeric Aβ forms a β-hairpin when bound to the affibody.	INTRO
49	58	β-hairpin	structure_element	The structure revealed that monomeric Aβ forms a β-hairpin when bound to the affibody.	INTRO
64	72	bound to	protein_state	The structure revealed that monomeric Aβ forms a β-hairpin when bound to the affibody.	INTRO
77	85	affibody	chemical	The structure revealed that monomeric Aβ forms a β-hairpin when bound to the affibody.	INTRO
5	7	Aβ	protein	This Aβ β-hairpin encompasses residues 17–37 and contains two β-strands comprising Aβ17–24 and Aβ30–37 connected by an Aβ25–29 loop.	INTRO
8	17	β-hairpin	structure_element	This Aβ β-hairpin encompasses residues 17–37 and contains two β-strands comprising Aβ17–24 and Aβ30–37 connected by an Aβ25–29 loop.	INTRO
39	44	17–37	residue_range	This Aβ β-hairpin encompasses residues 17–37 and contains two β-strands comprising Aβ17–24 and Aβ30–37 connected by an Aβ25–29 loop.	INTRO
62	71	β-strands	structure_element	This Aβ β-hairpin encompasses residues 17–37 and contains two β-strands comprising Aβ17–24 and Aβ30–37 connected by an Aβ25–29 loop.	INTRO
83	85	Aβ	protein	This Aβ β-hairpin encompasses residues 17–37 and contains two β-strands comprising Aβ17–24 and Aβ30–37 connected by an Aβ25–29 loop.	INTRO
85	90	17–24	residue_range	This Aβ β-hairpin encompasses residues 17–37 and contains two β-strands comprising Aβ17–24 and Aβ30–37 connected by an Aβ25–29 loop.	INTRO
95	97	Aβ	protein	This Aβ β-hairpin encompasses residues 17–37 and contains two β-strands comprising Aβ17–24 and Aβ30–37 connected by an Aβ25–29 loop.	INTRO
97	102	30–37	residue_range	This Aβ β-hairpin encompasses residues 17–37 and contains two β-strands comprising Aβ17–24 and Aβ30–37 connected by an Aβ25–29 loop.	INTRO
119	121	Aβ	protein	This Aβ β-hairpin encompasses residues 17–37 and contains two β-strands comprising Aβ17–24 and Aβ30–37 connected by an Aβ25–29 loop.	INTRO
121	126	25–29	residue_range	This Aβ β-hairpin encompasses residues 17–37 and contains two β-strands comprising Aβ17–24 and Aβ30–37 connected by an Aβ25–29 loop.	INTRO
127	131	loop	structure_element	This Aβ β-hairpin encompasses residues 17–37 and contains two β-strands comprising Aβ17–24 and Aβ30–37 connected by an Aβ25–29 loop.	INTRO
13	15	Aβ	protein	Sequestering Aβ within the affibody prevents its fibrilization and reduces its neurotoxicity, providing evidence that the β-hairpin structure may contribute to the ability of Aβ to form neurotoxic oligomers.	INTRO
27	35	affibody	chemical	Sequestering Aβ within the affibody prevents its fibrilization and reduces its neurotoxicity, providing evidence that the β-hairpin structure may contribute to the ability of Aβ to form neurotoxic oligomers.	INTRO
122	131	β-hairpin	structure_element	Sequestering Aβ within the affibody prevents its fibrilization and reduces its neurotoxicity, providing evidence that the β-hairpin structure may contribute to the ability of Aβ to form neurotoxic oligomers.	INTRO
175	177	Aβ	protein	Sequestering Aβ within the affibody prevents its fibrilization and reduces its neurotoxicity, providing evidence that the β-hairpin structure may contribute to the ability of Aβ to form neurotoxic oligomers.	INTRO
197	206	oligomers	oligomeric_state	Sequestering Aβ within the affibody prevents its fibrilization and reduces its neurotoxicity, providing evidence that the β-hairpin structure may contribute to the ability of Aβ to form neurotoxic oligomers.	INTRO
48	50	Aβ	protein	In a related study, Sandberg et al. constrained Aβ in a β-hairpin conformation by mutating residues A21 and A30 to cysteine and forming an intramolecular disulfide bond.	INTRO
56	65	β-hairpin	structure_element	In a related study, Sandberg et al. constrained Aβ in a β-hairpin conformation by mutating residues A21 and A30 to cysteine and forming an intramolecular disulfide bond.	INTRO
82	90	mutating	experimental_method	In a related study, Sandberg et al. constrained Aβ in a β-hairpin conformation by mutating residues A21 and A30 to cysteine and forming an intramolecular disulfide bond.	INTRO
100	103	A21	residue_name_number	In a related study, Sandberg et al. constrained Aβ in a β-hairpin conformation by mutating residues A21 and A30 to cysteine and forming an intramolecular disulfide bond.	INTRO
108	111	A30	residue_name_number	In a related study, Sandberg et al. constrained Aβ in a β-hairpin conformation by mutating residues A21 and A30 to cysteine and forming an intramolecular disulfide bond.	INTRO
115	123	cysteine	residue_name	In a related study, Sandberg et al. constrained Aβ in a β-hairpin conformation by mutating residues A21 and A30 to cysteine and forming an intramolecular disulfide bond.	INTRO
154	168	disulfide bond	ptm	In a related study, Sandberg et al. constrained Aβ in a β-hairpin conformation by mutating residues A21 and A30 to cysteine and forming an intramolecular disulfide bond.	INTRO
8	10	Aβ	protein	Locking Aβ into a β-hairpin structure resulted in the formation Aβ oligomers, which were observed by size exclusion chromatography (SEC) and SDS-PAGE.	INTRO
18	27	β-hairpin	structure_element	Locking Aβ into a β-hairpin structure resulted in the formation Aβ oligomers, which were observed by size exclusion chromatography (SEC) and SDS-PAGE.	INTRO
64	66	Aβ	protein	Locking Aβ into a β-hairpin structure resulted in the formation Aβ oligomers, which were observed by size exclusion chromatography (SEC) and SDS-PAGE.	INTRO
67	76	oligomers	oligomeric_state	Locking Aβ into a β-hairpin structure resulted in the formation Aβ oligomers, which were observed by size exclusion chromatography (SEC) and SDS-PAGE.	INTRO
101	130	size exclusion chromatography	experimental_method	Locking Aβ into a β-hairpin structure resulted in the formation Aβ oligomers, which were observed by size exclusion chromatography (SEC) and SDS-PAGE.	INTRO
132	135	SEC	experimental_method	Locking Aβ into a β-hairpin structure resulted in the formation Aβ oligomers, which were observed by size exclusion chromatography (SEC) and SDS-PAGE.	INTRO
141	149	SDS-PAGE	experimental_method	Locking Aβ into a β-hairpin structure resulted in the formation Aβ oligomers, which were observed by size exclusion chromatography (SEC) and SDS-PAGE.	INTRO
4	13	oligomers	oligomeric_state	The oligomers with a molecular weight of ∼100 kDa that were isolated by SEC were toxic toward neuronally derived SH-SY5Y cells.	INTRO
72	75	SEC	experimental_method	The oligomers with a molecular weight of ∼100 kDa that were isolated by SEC were toxic toward neuronally derived SH-SY5Y cells.	INTRO
45	54	β-hairpin	structure_element	This study provides evidence for the role of β-hairpin structure in Aβ oligomerization and neurotoxicity.	INTRO
68	70	Aβ	protein	This study provides evidence for the role of β-hairpin structure in Aβ oligomerization and neurotoxicity.	INTRO
18	27	β-hairpin	structure_element	Inspired by these β-hairpin structures, our laboratory developed a macrocyclic β-sheet peptide derived from Aβ17–36 designed to mimic an Aβ β-hairpin and reported its X-ray crystallographic structure.	INTRO
28	38	structures	evidence	Inspired by these β-hairpin structures, our laboratory developed a macrocyclic β-sheet peptide derived from Aβ17–36 designed to mimic an Aβ β-hairpin and reported its X-ray crystallographic structure.	INTRO
79	86	β-sheet	structure_element	Inspired by these β-hairpin structures, our laboratory developed a macrocyclic β-sheet peptide derived from Aβ17–36 designed to mimic an Aβ β-hairpin and reported its X-ray crystallographic structure.	INTRO
108	110	Aβ	protein	Inspired by these β-hairpin structures, our laboratory developed a macrocyclic β-sheet peptide derived from Aβ17–36 designed to mimic an Aβ β-hairpin and reported its X-ray crystallographic structure.	INTRO
110	115	17–36	residue_range	Inspired by these β-hairpin structures, our laboratory developed a macrocyclic β-sheet peptide derived from Aβ17–36 designed to mimic an Aβ β-hairpin and reported its X-ray crystallographic structure.	INTRO
137	139	Aβ	protein	Inspired by these β-hairpin structures, our laboratory developed a macrocyclic β-sheet peptide derived from Aβ17–36 designed to mimic an Aβ β-hairpin and reported its X-ray crystallographic structure.	INTRO
140	149	β-hairpin	structure_element	Inspired by these β-hairpin structures, our laboratory developed a macrocyclic β-sheet peptide derived from Aβ17–36 designed to mimic an Aβ β-hairpin and reported its X-ray crystallographic structure.	INTRO
167	199	X-ray crystallographic structure	evidence	Inspired by these β-hairpin structures, our laboratory developed a macrocyclic β-sheet peptide derived from Aβ17–36 designed to mimic an Aβ β-hairpin and reported its X-ray crystallographic structure.	INTRO
14	23	peptide 1	mutant	This peptide (peptide 1) consists of two β-strands comprising Aβ17–23 and Aβ30–36 covalently linked by two δ-linked ornithine (δOrn) β-turn mimics.	INTRO
41	50	β-strands	structure_element	This peptide (peptide 1) consists of two β-strands comprising Aβ17–23 and Aβ30–36 covalently linked by two δ-linked ornithine (δOrn) β-turn mimics.	INTRO
62	64	Aβ	protein	This peptide (peptide 1) consists of two β-strands comprising Aβ17–23 and Aβ30–36 covalently linked by two δ-linked ornithine (δOrn) β-turn mimics.	INTRO
64	69	17–23	residue_range	This peptide (peptide 1) consists of two β-strands comprising Aβ17–23 and Aβ30–36 covalently linked by two δ-linked ornithine (δOrn) β-turn mimics.	INTRO
74	76	Aβ	protein	This peptide (peptide 1) consists of two β-strands comprising Aβ17–23 and Aβ30–36 covalently linked by two δ-linked ornithine (δOrn) β-turn mimics.	INTRO
76	81	30–36	residue_range	This peptide (peptide 1) consists of two β-strands comprising Aβ17–23 and Aβ30–36 covalently linked by two δ-linked ornithine (δOrn) β-turn mimics.	INTRO
107	115	δ-linked	protein_state	This peptide (peptide 1) consists of two β-strands comprising Aβ17–23 and Aβ30–36 covalently linked by two δ-linked ornithine (δOrn) β-turn mimics.	INTRO
116	125	ornithine	residue_name	This peptide (peptide 1) consists of two β-strands comprising Aβ17–23 and Aβ30–36 covalently linked by two δ-linked ornithine (δOrn) β-turn mimics.	INTRO
127	131	δOrn	structure_element	This peptide (peptide 1) consists of two β-strands comprising Aβ17–23 and Aβ30–36 covalently linked by two δ-linked ornithine (δOrn) β-turn mimics.	INTRO
133	139	β-turn	structure_element	This peptide (peptide 1) consists of two β-strands comprising Aβ17–23 and Aβ30–36 covalently linked by two δ-linked ornithine (δOrn) β-turn mimics.	INTRO
4	8	δOrn	structure_element	The δOrn that connects residues D23 and A30 replaces the Aβ24–29 loop.	INTRO
32	35	D23	residue_name_number	The δOrn that connects residues D23 and A30 replaces the Aβ24–29 loop.	INTRO
40	43	A30	residue_name_number	The δOrn that connects residues D23 and A30 replaces the Aβ24–29 loop.	INTRO
57	59	Aβ	protein	The δOrn that connects residues D23 and A30 replaces the Aβ24–29 loop.	INTRO
59	64	24–29	residue_range	The δOrn that connects residues D23 and A30 replaces the Aβ24–29 loop.	INTRO
65	69	loop	structure_element	The δOrn that connects residues D23 and A30 replaces the Aβ24–29 loop.	INTRO
4	8	δOrn	structure_element	The δOrn that connects residues L17 and V36 enforces β-hairpin structure.	INTRO
32	35	L17	residue_name_number	The δOrn that connects residues L17 and V36 enforces β-hairpin structure.	INTRO
40	43	V36	residue_name_number	The δOrn that connects residues L17 and V36 enforces β-hairpin structure.	INTRO
53	62	β-hairpin	structure_element	The δOrn that connects residues L17 and V36 enforces β-hairpin structure.	INTRO
46	49	G33	residue_name_number	We incorporated an N-methyl group at position G33 to prevent uncontrolled aggregation and precipitation of the peptide.	INTRO
44	52	replaced	experimental_method	To improve the solubility of the peptide we replaced M35 with the hydrophilic isostere of methionine, ornithine (α-linked) (Figure 1B).	INTRO
53	56	M35	residue_name_number	To improve the solubility of the peptide we replaced M35 with the hydrophilic isostere of methionine, ornithine (α-linked) (Figure 1B).	INTRO
90	100	methionine	residue_name	To improve the solubility of the peptide we replaced M35 with the hydrophilic isostere of methionine, ornithine (α-linked) (Figure 1B).	INTRO
102	111	ornithine	residue_name	To improve the solubility of the peptide we replaced M35 with the hydrophilic isostere of methionine, ornithine (α-linked) (Figure 1B).	INTRO
113	121	α-linked	protein_state	To improve the solubility of the peptide we replaced M35 with the hydrophilic isostere of methionine, ornithine (α-linked) (Figure 1B).	INTRO
4	36	X-ray crystallographic structure	evidence	The X-ray crystallographic structure of peptide 1 reveals that it folds to form a β-hairpin that assembles to form trimers and that the trimers further assemble to form hexamers and dodecamers.	INTRO
40	49	peptide 1	mutant	The X-ray crystallographic structure of peptide 1 reveals that it folds to form a β-hairpin that assembles to form trimers and that the trimers further assemble to form hexamers and dodecamers.	INTRO
82	91	β-hairpin	structure_element	The X-ray crystallographic structure of peptide 1 reveals that it folds to form a β-hairpin that assembles to form trimers and that the trimers further assemble to form hexamers and dodecamers.	INTRO
115	122	trimers	oligomeric_state	The X-ray crystallographic structure of peptide 1 reveals that it folds to form a β-hairpin that assembles to form trimers and that the trimers further assemble to form hexamers and dodecamers.	INTRO
136	143	trimers	oligomeric_state	The X-ray crystallographic structure of peptide 1 reveals that it folds to form a β-hairpin that assembles to form trimers and that the trimers further assemble to form hexamers and dodecamers.	INTRO
169	177	hexamers	oligomeric_state	The X-ray crystallographic structure of peptide 1 reveals that it folds to form a β-hairpin that assembles to form trimers and that the trimers further assemble to form hexamers and dodecamers.	INTRO
182	192	dodecamers	oligomeric_state	The X-ray crystallographic structure of peptide 1 reveals that it folds to form a β-hairpin that assembles to form trimers and that the trimers further assemble to form hexamers and dodecamers.	INTRO
39	55	peptides 1 and 2	chemical	(A) Cartoon illustrating the design of peptides 1 and 2 and their relationship to an Aβ17–36 β-hairpin.	FIG
85	87	Aβ	protein	(A) Cartoon illustrating the design of peptides 1 and 2 and their relationship to an Aβ17–36 β-hairpin.	FIG
87	92	17–36	residue_range	(A) Cartoon illustrating the design of peptides 1 and 2 and their relationship to an Aβ17–36 β-hairpin.	FIG
93	102	β-hairpin	structure_element	(A) Cartoon illustrating the design of peptides 1 and 2 and their relationship to an Aβ17–36 β-hairpin.	FIG
27	36	peptide 1	mutant	 (B) Chemical structure of peptide 1 illustrating Aβ17–23 and Aβ30–36, M35Orn, the N-methyl group, and the δ-linked ornithine turns. (C) Chemical structure of peptide 2 illustrating Aβ17–36, the N-methyl group, the disulfide bond across positions 24 and 29, and the δ-linked ornithine turn.	FIG
50	52	Aβ	protein	 (B) Chemical structure of peptide 1 illustrating Aβ17–23 and Aβ30–36, M35Orn, the N-methyl group, and the δ-linked ornithine turns. (C) Chemical structure of peptide 2 illustrating Aβ17–36, the N-methyl group, the disulfide bond across positions 24 and 29, and the δ-linked ornithine turn.	FIG
62	64	Aβ	protein	 (B) Chemical structure of peptide 1 illustrating Aβ17–23 and Aβ30–36, M35Orn, the N-methyl group, and the δ-linked ornithine turns. (C) Chemical structure of peptide 2 illustrating Aβ17–36, the N-methyl group, the disulfide bond across positions 24 and 29, and the δ-linked ornithine turn.	FIG
107	115	δ-linked	protein_state	 (B) Chemical structure of peptide 1 illustrating Aβ17–23 and Aβ30–36, M35Orn, the N-methyl group, and the δ-linked ornithine turns. (C) Chemical structure of peptide 2 illustrating Aβ17–36, the N-methyl group, the disulfide bond across positions 24 and 29, and the δ-linked ornithine turn.	FIG
116	125	ornithine	residue_name	 (B) Chemical structure of peptide 1 illustrating Aβ17–23 and Aβ30–36, M35Orn, the N-methyl group, and the δ-linked ornithine turns. (C) Chemical structure of peptide 2 illustrating Aβ17–36, the N-methyl group, the disulfide bond across positions 24 and 29, and the δ-linked ornithine turn.	FIG
126	131	turns	structure_element	 (B) Chemical structure of peptide 1 illustrating Aβ17–23 and Aβ30–36, M35Orn, the N-methyl group, and the δ-linked ornithine turns. (C) Chemical structure of peptide 2 illustrating Aβ17–36, the N-methyl group, the disulfide bond across positions 24 and 29, and the δ-linked ornithine turn.	FIG
159	168	peptide 2	mutant	 (B) Chemical structure of peptide 1 illustrating Aβ17–23 and Aβ30–36, M35Orn, the N-methyl group, and the δ-linked ornithine turns. (C) Chemical structure of peptide 2 illustrating Aβ17–36, the N-methyl group, the disulfide bond across positions 24 and 29, and the δ-linked ornithine turn.	FIG
182	184	Aβ	protein	 (B) Chemical structure of peptide 1 illustrating Aβ17–23 and Aβ30–36, M35Orn, the N-methyl group, and the δ-linked ornithine turns. (C) Chemical structure of peptide 2 illustrating Aβ17–36, the N-methyl group, the disulfide bond across positions 24 and 29, and the δ-linked ornithine turn.	FIG
215	229	disulfide bond	ptm	 (B) Chemical structure of peptide 1 illustrating Aβ17–23 and Aβ30–36, M35Orn, the N-methyl group, and the δ-linked ornithine turns. (C) Chemical structure of peptide 2 illustrating Aβ17–36, the N-methyl group, the disulfide bond across positions 24 and 29, and the δ-linked ornithine turn.	FIG
247	249	24	residue_number	 (B) Chemical structure of peptide 1 illustrating Aβ17–23 and Aβ30–36, M35Orn, the N-methyl group, and the δ-linked ornithine turns. (C) Chemical structure of peptide 2 illustrating Aβ17–36, the N-methyl group, the disulfide bond across positions 24 and 29, and the δ-linked ornithine turn.	FIG
254	256	29	residue_number	 (B) Chemical structure of peptide 1 illustrating Aβ17–23 and Aβ30–36, M35Orn, the N-methyl group, and the δ-linked ornithine turns. (C) Chemical structure of peptide 2 illustrating Aβ17–36, the N-methyl group, the disulfide bond across positions 24 and 29, and the δ-linked ornithine turn.	FIG
266	274	δ-linked	protein_state	 (B) Chemical structure of peptide 1 illustrating Aβ17–23 and Aβ30–36, M35Orn, the N-methyl group, and the δ-linked ornithine turns. (C) Chemical structure of peptide 2 illustrating Aβ17–36, the N-methyl group, the disulfide bond across positions 24 and 29, and the δ-linked ornithine turn.	FIG
275	284	ornithine	residue_name	 (B) Chemical structure of peptide 1 illustrating Aβ17–23 and Aβ30–36, M35Orn, the N-methyl group, and the δ-linked ornithine turns. (C) Chemical structure of peptide 2 illustrating Aβ17–36, the N-methyl group, the disulfide bond across positions 24 and 29, and the δ-linked ornithine turn.	FIG
285	289	turn	structure_element	 (B) Chemical structure of peptide 1 illustrating Aβ17–23 and Aβ30–36, M35Orn, the N-methyl group, and the δ-linked ornithine turns. (C) Chemical structure of peptide 2 illustrating Aβ17–36, the N-methyl group, the disulfide bond across positions 24 and 29, and the δ-linked ornithine turn.	FIG
14	23	peptide 1	mutant	Our design of peptide 1 omitted the Aβ24–29 loop.	INTRO
36	38	Aβ	protein	Our design of peptide 1 omitted the Aβ24–29 loop.	INTRO
38	43	24–29	residue_range	Our design of peptide 1 omitted the Aβ24–29 loop.	INTRO
44	48	loop	structure_element	Our design of peptide 1 omitted the Aβ24–29 loop.	INTRO
17	19	Aβ	protein	To visualize the Aβ24–29 loop, we performed replica-exchange molecular dynamics (REMD) simulations on Aβ17–36 using the X-ray crystallographic coordinates of Aβ17–23 and Aβ30–36 from peptide 1.	INTRO
19	24	24–29	residue_range	To visualize the Aβ24–29 loop, we performed replica-exchange molecular dynamics (REMD) simulations on Aβ17–36 using the X-ray crystallographic coordinates of Aβ17–23 and Aβ30–36 from peptide 1.	INTRO
25	29	loop	structure_element	To visualize the Aβ24–29 loop, we performed replica-exchange molecular dynamics (REMD) simulations on Aβ17–36 using the X-ray crystallographic coordinates of Aβ17–23 and Aβ30–36 from peptide 1.	INTRO
44	79	replica-exchange molecular dynamics	experimental_method	To visualize the Aβ24–29 loop, we performed replica-exchange molecular dynamics (REMD) simulations on Aβ17–36 using the X-ray crystallographic coordinates of Aβ17–23 and Aβ30–36 from peptide 1.	INTRO
81	85	REMD	experimental_method	To visualize the Aβ24–29 loop, we performed replica-exchange molecular dynamics (REMD) simulations on Aβ17–36 using the X-ray crystallographic coordinates of Aβ17–23 and Aβ30–36 from peptide 1.	INTRO
87	98	simulations	experimental_method	To visualize the Aβ24–29 loop, we performed replica-exchange molecular dynamics (REMD) simulations on Aβ17–36 using the X-ray crystallographic coordinates of Aβ17–23 and Aβ30–36 from peptide 1.	INTRO
102	104	Aβ	protein	To visualize the Aβ24–29 loop, we performed replica-exchange molecular dynamics (REMD) simulations on Aβ17–36 using the X-ray crystallographic coordinates of Aβ17–23 and Aβ30–36 from peptide 1.	INTRO
104	109	17–36	residue_range	To visualize the Aβ24–29 loop, we performed replica-exchange molecular dynamics (REMD) simulations on Aβ17–36 using the X-ray crystallographic coordinates of Aβ17–23 and Aβ30–36 from peptide 1.	INTRO
120	154	X-ray crystallographic coordinates	evidence	To visualize the Aβ24–29 loop, we performed replica-exchange molecular dynamics (REMD) simulations on Aβ17–36 using the X-ray crystallographic coordinates of Aβ17–23 and Aβ30–36 from peptide 1.	INTRO
158	160	Aβ	protein	To visualize the Aβ24–29 loop, we performed replica-exchange molecular dynamics (REMD) simulations on Aβ17–36 using the X-ray crystallographic coordinates of Aβ17–23 and Aβ30–36 from peptide 1.	INTRO
160	165	17–23	residue_range	To visualize the Aβ24–29 loop, we performed replica-exchange molecular dynamics (REMD) simulations on Aβ17–36 using the X-ray crystallographic coordinates of Aβ17–23 and Aβ30–36 from peptide 1.	INTRO
170	172	Aβ	protein	To visualize the Aβ24–29 loop, we performed replica-exchange molecular dynamics (REMD) simulations on Aβ17–36 using the X-ray crystallographic coordinates of Aβ17–23 and Aβ30–36 from peptide 1.	INTRO
172	177	30–36	residue_range	To visualize the Aβ24–29 loop, we performed replica-exchange molecular dynamics (REMD) simulations on Aβ17–36 using the X-ray crystallographic coordinates of Aβ17–23 and Aβ30–36 from peptide 1.	INTRO
183	192	peptide 1	mutant	To visualize the Aβ24–29 loop, we performed replica-exchange molecular dynamics (REMD) simulations on Aβ17–36 using the X-ray crystallographic coordinates of Aβ17–23 and Aβ30–36 from peptide 1.	INTRO
45	51	trimer	oligomeric_state	These studies provided a working model for a trimer of Aβ17–36 β-hairpins and demonstrated that the trimer should be capable of accommodating the Aβ24–29 loop.	INTRO
55	57	Aβ	protein	These studies provided a working model for a trimer of Aβ17–36 β-hairpins and demonstrated that the trimer should be capable of accommodating the Aβ24–29 loop.	INTRO
57	62	17–36	residue_range	These studies provided a working model for a trimer of Aβ17–36 β-hairpins and demonstrated that the trimer should be capable of accommodating the Aβ24–29 loop.	INTRO
63	73	β-hairpins	structure_element	These studies provided a working model for a trimer of Aβ17–36 β-hairpins and demonstrated that the trimer should be capable of accommodating the Aβ24–29 loop.	INTRO
100	106	trimer	oligomeric_state	These studies provided a working model for a trimer of Aβ17–36 β-hairpins and demonstrated that the trimer should be capable of accommodating the Aβ24–29 loop.	INTRO
146	148	Aβ	protein	These studies provided a working model for a trimer of Aβ17–36 β-hairpins and demonstrated that the trimer should be capable of accommodating the Aβ24–29 loop.	INTRO
148	153	24–29	residue_range	These studies provided a working model for a trimer of Aβ17–36 β-hairpins and demonstrated that the trimer should be capable of accommodating the Aβ24–29 loop.	INTRO
154	158	loop	structure_element	These studies provided a working model for a trimer of Aβ17–36 β-hairpins and demonstrated that the trimer should be capable of accommodating the Aβ24–29 loop.	INTRO
35	42	restore	experimental_method	In the current study we set out to restore the Aβ24–29 loop, reintroduce the methionine residue at position 35, and determine the X-ray crystallographic structures of oligomers that form.	INTRO
47	49	Aβ	protein	In the current study we set out to restore the Aβ24–29 loop, reintroduce the methionine residue at position 35, and determine the X-ray crystallographic structures of oligomers that form.	INTRO
49	54	24–29	residue_range	In the current study we set out to restore the Aβ24–29 loop, reintroduce the methionine residue at position 35, and determine the X-ray crystallographic structures of oligomers that form.	INTRO
55	59	loop	structure_element	In the current study we set out to restore the Aβ24–29 loop, reintroduce the methionine residue at position 35, and determine the X-ray crystallographic structures of oligomers that form.	INTRO
61	72	reintroduce	experimental_method	In the current study we set out to restore the Aβ24–29 loop, reintroduce the methionine residue at position 35, and determine the X-ray crystallographic structures of oligomers that form.	INTRO
77	87	methionine	residue_name	In the current study we set out to restore the Aβ24–29 loop, reintroduce the methionine residue at position 35, and determine the X-ray crystallographic structures of oligomers that form.	INTRO
108	110	35	residue_number	In the current study we set out to restore the Aβ24–29 loop, reintroduce the methionine residue at position 35, and determine the X-ray crystallographic structures of oligomers that form.	INTRO
130	163	X-ray crystallographic structures	evidence	In the current study we set out to restore the Aβ24–29 loop, reintroduce the methionine residue at position 35, and determine the X-ray crystallographic structures of oligomers that form.	INTRO
167	176	oligomers	oligomeric_state	In the current study we set out to restore the Aβ24–29 loop, reintroduce the methionine residue at position 35, and determine the X-ray crystallographic structures of oligomers that form.	INTRO
12	21	peptide 2	mutant	We designed peptide 2 as a homologue of peptide 1 that embodies these ideas.	INTRO
40	49	peptide 1	mutant	We designed peptide 2 as a homologue of peptide 1 that embodies these ideas.	INTRO
0	9	Peptide 2	mutant	Peptide 2 contains a methionine residue at position 35 and an Aβ24–29 loop with residues 24 and 29 (Val and Gly) mutated to cysteine and linked by a disulfide bond (Figure 1C).	INTRO
21	31	methionine	residue_name	Peptide 2 contains a methionine residue at position 35 and an Aβ24–29 loop with residues 24 and 29 (Val and Gly) mutated to cysteine and linked by a disulfide bond (Figure 1C).	INTRO
52	54	35	residue_number	Peptide 2 contains a methionine residue at position 35 and an Aβ24–29 loop with residues 24 and 29 (Val and Gly) mutated to cysteine and linked by a disulfide bond (Figure 1C).	INTRO
62	64	Aβ	protein	Peptide 2 contains a methionine residue at position 35 and an Aβ24–29 loop with residues 24 and 29 (Val and Gly) mutated to cysteine and linked by a disulfide bond (Figure 1C).	INTRO
64	69	24–29	residue_range	Peptide 2 contains a methionine residue at position 35 and an Aβ24–29 loop with residues 24 and 29 (Val and Gly) mutated to cysteine and linked by a disulfide bond (Figure 1C).	INTRO
70	74	loop	structure_element	Peptide 2 contains a methionine residue at position 35 and an Aβ24–29 loop with residues 24 and 29 (Val and Gly) mutated to cysteine and linked by a disulfide bond (Figure 1C).	INTRO
89	91	24	residue_number	Peptide 2 contains a methionine residue at position 35 and an Aβ24–29 loop with residues 24 and 29 (Val and Gly) mutated to cysteine and linked by a disulfide bond (Figure 1C).	INTRO
96	98	29	residue_number	Peptide 2 contains a methionine residue at position 35 and an Aβ24–29 loop with residues 24 and 29 (Val and Gly) mutated to cysteine and linked by a disulfide bond (Figure 1C).	INTRO
100	103	Val	residue_name	Peptide 2 contains a methionine residue at position 35 and an Aβ24–29 loop with residues 24 and 29 (Val and Gly) mutated to cysteine and linked by a disulfide bond (Figure 1C).	INTRO
108	111	Gly	residue_name	Peptide 2 contains a methionine residue at position 35 and an Aβ24–29 loop with residues 24 and 29 (Val and Gly) mutated to cysteine and linked by a disulfide bond (Figure 1C).	INTRO
113	120	mutated	experimental_method	Peptide 2 contains a methionine residue at position 35 and an Aβ24–29 loop with residues 24 and 29 (Val and Gly) mutated to cysteine and linked by a disulfide bond (Figure 1C).	INTRO
124	132	cysteine	residue_name	Peptide 2 contains a methionine residue at position 35 and an Aβ24–29 loop with residues 24 and 29 (Val and Gly) mutated to cysteine and linked by a disulfide bond (Figure 1C).	INTRO
149	163	disulfide bond	ptm	Peptide 2 contains a methionine residue at position 35 and an Aβ24–29 loop with residues 24 and 29 (Val and Gly) mutated to cysteine and linked by a disulfide bond (Figure 1C).	INTRO
37	46	peptide 2	mutant	Here, we describe the development of peptide 2 and report the X-ray crystallographic structures of the trimer, dodecamer, and annular pore observed within the crystal structure.	INTRO
62	95	X-ray crystallographic structures	evidence	Here, we describe the development of peptide 2 and report the X-ray crystallographic structures of the trimer, dodecamer, and annular pore observed within the crystal structure.	INTRO
103	109	trimer	oligomeric_state	Here, we describe the development of peptide 2 and report the X-ray crystallographic structures of the trimer, dodecamer, and annular pore observed within the crystal structure.	INTRO
111	120	dodecamer	oligomeric_state	Here, we describe the development of peptide 2 and report the X-ray crystallographic structures of the trimer, dodecamer, and annular pore observed within the crystal structure.	INTRO
126	138	annular pore	site	Here, we describe the development of peptide 2 and report the X-ray crystallographic structures of the trimer, dodecamer, and annular pore observed within the crystal structure.	INTRO
159	176	crystal structure	evidence	Here, we describe the development of peptide 2 and report the X-ray crystallographic structures of the trimer, dodecamer, and annular pore observed within the crystal structure.	INTRO
15	24	Peptide 2	mutant	Development of Peptide 2	RESULTS
13	22	peptide 2	mutant	We developed peptide 2 from peptide 1 by an iterative process, in which we first attempted to restore the Aβ24–29 loop without a disulfide linkage.	RESULTS
28	37	peptide 1	mutant	We developed peptide 2 from peptide 1 by an iterative process, in which we first attempted to restore the Aβ24–29 loop without a disulfide linkage.	RESULTS
106	108	Aβ	protein	We developed peptide 2 from peptide 1 by an iterative process, in which we first attempted to restore the Aβ24–29 loop without a disulfide linkage.	RESULTS
108	113	24–29	residue_range	We developed peptide 2 from peptide 1 by an iterative process, in which we first attempted to restore the Aβ24–29 loop without a disulfide linkage.	RESULTS
114	118	loop	structure_element	We developed peptide 2 from peptide 1 by an iterative process, in which we first attempted to restore the Aβ24–29 loop without a disulfide linkage.	RESULTS
129	146	disulfide linkage	ptm	We developed peptide 2 from peptide 1 by an iterative process, in which we first attempted to restore the Aβ24–29 loop without a disulfide linkage.	RESULTS
14	23	peptide 3	mutant	We envisioned peptide 3 as a homologue of peptide 1 with the Aβ24–29 loop in place of the δOrn that connects D23 and A30 and p-iodophenylalanine (FI) in place of F19.	RESULTS
42	51	peptide 1	mutant	We envisioned peptide 3 as a homologue of peptide 1 with the Aβ24–29 loop in place of the δOrn that connects D23 and A30 and p-iodophenylalanine (FI) in place of F19.	RESULTS
61	63	Aβ	protein	We envisioned peptide 3 as a homologue of peptide 1 with the Aβ24–29 loop in place of the δOrn that connects D23 and A30 and p-iodophenylalanine (FI) in place of F19.	RESULTS
63	68	24–29	residue_range	We envisioned peptide 3 as a homologue of peptide 1 with the Aβ24–29 loop in place of the δOrn that connects D23 and A30 and p-iodophenylalanine (FI) in place of F19.	RESULTS
69	73	loop	structure_element	We envisioned peptide 3 as a homologue of peptide 1 with the Aβ24–29 loop in place of the δOrn that connects D23 and A30 and p-iodophenylalanine (FI) in place of F19.	RESULTS
90	94	δOrn	structure_element	We envisioned peptide 3 as a homologue of peptide 1 with the Aβ24–29 loop in place of the δOrn that connects D23 and A30 and p-iodophenylalanine (FI) in place of F19.	RESULTS
109	112	D23	residue_name_number	We envisioned peptide 3 as a homologue of peptide 1 with the Aβ24–29 loop in place of the δOrn that connects D23 and A30 and p-iodophenylalanine (FI) in place of F19.	RESULTS
117	120	A30	residue_name_number	We envisioned peptide 3 as a homologue of peptide 1 with the Aβ24–29 loop in place of the δOrn that connects D23 and A30 and p-iodophenylalanine (FI) in place of F19.	RESULTS
125	144	p-iodophenylalanine	chemical	We envisioned peptide 3 as a homologue of peptide 1 with the Aβ24–29 loop in place of the δOrn that connects D23 and A30 and p-iodophenylalanine (FI) in place of F19.	RESULTS
146	148	FI	chemical	We envisioned peptide 3 as a homologue of peptide 1 with the Aβ24–29 loop in place of the δOrn that connects D23 and A30 and p-iodophenylalanine (FI) in place of F19.	RESULTS
162	165	F19	residue_name_number	We envisioned peptide 3 as a homologue of peptide 1 with the Aβ24–29 loop in place of the δOrn that connects D23 and A30 and p-iodophenylalanine (FI) in place of F19.	RESULTS
17	36	p-iodophenylalanine	chemical	We routinely use p-iodophenylalanine to determine the X-ray crystallographic phases.	RESULTS
54	83	X-ray crystallographic phases	evidence	We routinely use p-iodophenylalanine to determine the X-ray crystallographic phases.	RESULTS
22	54	X-ray crystallographic structure	evidence	After determining the X-ray crystallographic structure of the p-iodophenylalanine variant we attempt to determine the structure of the native phenylalanine compound by isomorphous replacement.	RESULTS
62	81	p-iodophenylalanine	chemical	After determining the X-ray crystallographic structure of the p-iodophenylalanine variant we attempt to determine the structure of the native phenylalanine compound by isomorphous replacement.	RESULTS
118	127	structure	evidence	After determining the X-ray crystallographic structure of the p-iodophenylalanine variant we attempt to determine the structure of the native phenylalanine compound by isomorphous replacement.	RESULTS
142	155	phenylalanine	residue_name	After determining the X-ray crystallographic structure of the p-iodophenylalanine variant we attempt to determine the structure of the native phenylalanine compound by isomorphous replacement.	RESULTS
168	191	isomorphous replacement	experimental_method	After determining the X-ray crystallographic structure of the p-iodophenylalanine variant we attempt to determine the structure of the native phenylalanine compound by isomorphous replacement.	RESULTS
18	27	peptide 3	mutant	Upon synthesizing peptide 3, we found that it formed an amorphous precipitate in most crystallization conditions screened and failed to afford crystals in any condition.	RESULTS
143	151	crystals	evidence	Upon synthesizing peptide 3, we found that it formed an amorphous precipitate in most crystallization conditions screened and failed to afford crystals in any condition.	RESULTS
34	38	δOrn	structure_element	We postulate that the loss of the δOrn constraint leads to conformational heterogeneity that prevents peptide 3 from crystallizing.	RESULTS
102	111	peptide 3	mutant	We postulate that the loss of the δOrn constraint leads to conformational heterogeneity that prevents peptide 3 from crystallizing.	RESULTS
46	60	disulfide bond	ptm	To address this issue, we next incorporated a disulfide bond between residues 24 and 29 as a conformational constraint that serves as a surrogate for δOrn.	RESULTS
78	80	24	residue_number	To address this issue, we next incorporated a disulfide bond between residues 24 and 29 as a conformational constraint that serves as a surrogate for δOrn.	RESULTS
85	87	29	residue_number	To address this issue, we next incorporated a disulfide bond between residues 24 and 29 as a conformational constraint that serves as a surrogate for δOrn.	RESULTS
150	154	δOrn	structure_element	To address this issue, we next incorporated a disulfide bond between residues 24 and 29 as a conformational constraint that serves as a surrogate for δOrn.	RESULTS
12	21	peptide 4	mutant	We designed peptide 4 to embody this idea, mutating Val24 and Gly29 to cysteine and forming an interstrand disulfide linkage.	RESULTS
43	51	mutating	experimental_method	We designed peptide 4 to embody this idea, mutating Val24 and Gly29 to cysteine and forming an interstrand disulfide linkage.	RESULTS
52	57	Val24	residue_name_number	We designed peptide 4 to embody this idea, mutating Val24 and Gly29 to cysteine and forming an interstrand disulfide linkage.	RESULTS
62	67	Gly29	residue_name_number	We designed peptide 4 to embody this idea, mutating Val24 and Gly29 to cysteine and forming an interstrand disulfide linkage.	RESULTS
71	79	cysteine	residue_name	We designed peptide 4 to embody this idea, mutating Val24 and Gly29 to cysteine and forming an interstrand disulfide linkage.	RESULTS
107	124	disulfide linkage	ptm	We designed peptide 4 to embody this idea, mutating Val24 and Gly29 to cysteine and forming an interstrand disulfide linkage.	RESULTS
3	10	mutated	experimental_method	We mutated these residues because they occupy the same position as the δOrn that connects D23 and A30 in peptide 1.	RESULTS
71	75	δOrn	structure_element	We mutated these residues because they occupy the same position as the δOrn that connects D23 and A30 in peptide 1.	RESULTS
90	93	D23	residue_name_number	We mutated these residues because they occupy the same position as the δOrn that connects D23 and A30 in peptide 1.	RESULTS
98	101	A30	residue_name_number	We mutated these residues because they occupy the same position as the δOrn that connects D23 and A30 in peptide 1.	RESULTS
105	114	peptide 1	mutant	We mutated these residues because they occupy the same position as the δOrn that connects D23 and A30 in peptide 1.	RESULTS
9	12	V24	residue_name_number	Residues V24 and G29 form a non-hydrogen-bonded pair, which can readily accommodate disulfide linkages in antiparallel β-sheets.	RESULTS
17	20	G29	residue_name_number	Residues V24 and G29 form a non-hydrogen-bonded pair, which can readily accommodate disulfide linkages in antiparallel β-sheets.	RESULTS
28	52	non-hydrogen-bonded pair	bond_interaction	Residues V24 and G29 form a non-hydrogen-bonded pair, which can readily accommodate disulfide linkages in antiparallel β-sheets.	RESULTS
84	102	disulfide linkages	ptm	Residues V24 and G29 form a non-hydrogen-bonded pair, which can readily accommodate disulfide linkages in antiparallel β-sheets.	RESULTS
106	127	antiparallel β-sheets	structure_element	Residues V24 and G29 form a non-hydrogen-bonded pair, which can readily accommodate disulfide linkages in antiparallel β-sheets.	RESULTS
0	15	Disulfide bonds	ptm	Disulfide bonds across non-hydrogen-bonded pairs stabilize β-hairpins, while disulfide bonds across hydrogen-bonded pairs do not.	RESULTS
23	48	non-hydrogen-bonded pairs	bond_interaction	Disulfide bonds across non-hydrogen-bonded pairs stabilize β-hairpins, while disulfide bonds across hydrogen-bonded pairs do not.	RESULTS
59	69	β-hairpins	structure_element	Disulfide bonds across non-hydrogen-bonded pairs stabilize β-hairpins, while disulfide bonds across hydrogen-bonded pairs do not.	RESULTS
77	92	disulfide bonds	ptm	Disulfide bonds across non-hydrogen-bonded pairs stabilize β-hairpins, while disulfide bonds across hydrogen-bonded pairs do not.	RESULTS
100	121	hydrogen-bonded pairs	bond_interaction	Disulfide bonds across non-hydrogen-bonded pairs stabilize β-hairpins, while disulfide bonds across hydrogen-bonded pairs do not.	RESULTS
13	27	disulfide bond	ptm	Although the disulfide bond between positions 24 and 29 helps stabilize the β-hairpin, it does not alter the charge or substantially change the hydrophobicity of the Aβ17–36 β-hairpin.	RESULTS
46	48	24	residue_number	Although the disulfide bond between positions 24 and 29 helps stabilize the β-hairpin, it does not alter the charge or substantially change the hydrophobicity of the Aβ17–36 β-hairpin.	RESULTS
53	55	29	residue_number	Although the disulfide bond between positions 24 and 29 helps stabilize the β-hairpin, it does not alter the charge or substantially change the hydrophobicity of the Aβ17–36 β-hairpin.	RESULTS
76	85	β-hairpin	structure_element	Although the disulfide bond between positions 24 and 29 helps stabilize the β-hairpin, it does not alter the charge or substantially change the hydrophobicity of the Aβ17–36 β-hairpin.	RESULTS
166	168	Aβ	protein	Although the disulfide bond between positions 24 and 29 helps stabilize the β-hairpin, it does not alter the charge or substantially change the hydrophobicity of the Aβ17–36 β-hairpin.	RESULTS
168	173	17–36	residue_range	Although the disulfide bond between positions 24 and 29 helps stabilize the β-hairpin, it does not alter the charge or substantially change the hydrophobicity of the Aβ17–36 β-hairpin.	RESULTS
174	183	β-hairpin	structure_element	Although the disulfide bond between positions 24 and 29 helps stabilize the β-hairpin, it does not alter the charge or substantially change the hydrophobicity of the Aβ17–36 β-hairpin.	RESULTS
31	40	peptide 4	mutant	We were gratified to find that peptide 4 afforded crystals suitable for X-ray crystallography.	RESULTS
50	58	crystals	evidence	We were gratified to find that peptide 4 afforded crystals suitable for X-ray crystallography.	RESULTS
72	93	X-ray crystallography	experimental_method	We were gratified to find that peptide 4 afforded crystals suitable for X-ray crystallography.	RESULTS
46	56	determined	experimental_method	As the next step in the iterative process, we determined the X-ray crystallographic structure of this peptide (PDB 5HOW).	RESULTS
61	93	X-ray crystallographic structure	evidence	As the next step in the iterative process, we determined the X-ray crystallographic structure of this peptide (PDB 5HOW).	RESULTS
22	54	X-ray crystallographic structure	evidence	After determining the X-ray crystallographic structure of peptide 4 we reintroduced the native phenylalanine at position 19 and the methionine at position 35 to afford peptide 2.	RESULTS
58	67	peptide 4	mutant	After determining the X-ray crystallographic structure of peptide 4 we reintroduced the native phenylalanine at position 19 and the methionine at position 35 to afford peptide 2.	RESULTS
71	83	reintroduced	experimental_method	After determining the X-ray crystallographic structure of peptide 4 we reintroduced the native phenylalanine at position 19 and the methionine at position 35 to afford peptide 2.	RESULTS
95	108	phenylalanine	residue_name	After determining the X-ray crystallographic structure of peptide 4 we reintroduced the native phenylalanine at position 19 and the methionine at position 35 to afford peptide 2.	RESULTS
121	123	19	residue_number	After determining the X-ray crystallographic structure of peptide 4 we reintroduced the native phenylalanine at position 19 and the methionine at position 35 to afford peptide 2.	RESULTS
132	142	methionine	residue_name	After determining the X-ray crystallographic structure of peptide 4 we reintroduced the native phenylalanine at position 19 and the methionine at position 35 to afford peptide 2.	RESULTS
155	157	35	residue_number	After determining the X-ray crystallographic structure of peptide 4 we reintroduced the native phenylalanine at position 19 and the methionine at position 35 to afford peptide 2.	RESULTS
168	177	peptide 2	mutant	After determining the X-ray crystallographic structure of peptide 4 we reintroduced the native phenylalanine at position 19 and the methionine at position 35 to afford peptide 2.	RESULTS
89	121	X-ray crystallographic structure	evidence	We completed the iterative process—from 1 to 3 to 4 to 2—by successfully determining the X-ray crystallographic structure of peptide 2 (PDB 5HOX and 5HOY).	RESULTS
125	134	peptide 2	mutant	We completed the iterative process—from 1 to 3 to 4 to 2—by successfully determining the X-ray crystallographic structure of peptide 2 (PDB 5HOX and 5HOY).	RESULTS
49	61	peptides 2–4	mutant	The following sections describe the synthesis of peptides 2–4 and the X-ray crystallographic structure of peptide 2.	RESULTS
70	102	X-ray crystallographic structure	evidence	The following sections describe the synthesis of peptides 2–4 and the X-ray crystallographic structure of peptide 2.	RESULTS
106	115	peptide 2	mutant	The following sections describe the synthesis of peptides 2–4 and the X-ray crystallographic structure of peptide 2.	RESULTS
13	25	Peptides 2–4	mutant	Synthesis of Peptides 2–4	RESULTS
15	27	peptides 2–4	mutant	We synthesized peptides 2–4 by similar procedures to those we have developed for other macrocyclic peptides.	RESULTS
16	32	peptides 2 and 4	mutant	In synthesizing peptides 2 and 4 we formed the disulfide linkage after macrolactamization and deprotection of the acid-labile side chain protecting groups.	RESULTS
47	64	disulfide linkage	ptm	In synthesizing peptides 2 and 4 we formed the disulfide linkage after macrolactamization and deprotection of the acid-labile side chain protecting groups.	RESULTS
8	19	acid-stable	protein_state	We used acid-stable Acm-protected cysteine residues at positions 24 and 29 and removed the Acm groups by oxidation with I2 in aqueous acetic acid to afford the disulfide linkage.	RESULTS
20	33	Acm-protected	protein_state	We used acid-stable Acm-protected cysteine residues at positions 24 and 29 and removed the Acm groups by oxidation with I2 in aqueous acetic acid to afford the disulfide linkage.	RESULTS
34	42	cysteine	residue_name	We used acid-stable Acm-protected cysteine residues at positions 24 and 29 and removed the Acm groups by oxidation with I2 in aqueous acetic acid to afford the disulfide linkage.	RESULTS
65	67	24	residue_number	We used acid-stable Acm-protected cysteine residues at positions 24 and 29 and removed the Acm groups by oxidation with I2 in aqueous acetic acid to afford the disulfide linkage.	RESULTS
72	74	29	residue_number	We used acid-stable Acm-protected cysteine residues at positions 24 and 29 and removed the Acm groups by oxidation with I2 in aqueous acetic acid to afford the disulfide linkage.	RESULTS
134	145	acetic acid	chemical	We used acid-stable Acm-protected cysteine residues at positions 24 and 29 and removed the Acm groups by oxidation with I2 in aqueous acetic acid to afford the disulfide linkage.	RESULTS
160	177	disulfide linkage	ptm	We used acid-stable Acm-protected cysteine residues at positions 24 and 29 and removed the Acm groups by oxidation with I2 in aqueous acetic acid to afford the disulfide linkage.	RESULTS
0	12	Peptides 2–4	mutant	Peptides 2–4 were purified by RP-HPLC.	RESULTS
30	37	RP-HPLC	experimental_method	Peptides 2–4 were purified by RP-HPLC.	RESULTS
0	15	Crystallization	experimental_method	Crystallization, X-ray Crystallographic Data Collection, Data Processing, and Structure Determination of Peptides 2 and 4	RESULTS
17	55	X-ray Crystallographic Data Collection	experimental_method	Crystallization, X-ray Crystallographic Data Collection, Data Processing, and Structure Determination of Peptides 2 and 4	RESULTS
78	101	Structure Determination	experimental_method	Crystallization, X-ray Crystallographic Data Collection, Data Processing, and Structure Determination of Peptides 2 and 4	RESULTS
105	121	Peptides 2 and 4	mutant	Crystallization, X-ray Crystallographic Data Collection, Data Processing, and Structure Determination of Peptides 2 and 4	RESULTS
3	38	screened crystallization conditions	experimental_method	We screened crystallization conditions for peptide 4 in a 96-well-plate format using three different Hampton Research crystallization kits (Crystal Screen, Index, and PEG/Ion) with three ratios of peptide and mother liquor per condition (864 experiments).	RESULTS
43	52	peptide 4	mutant	We screened crystallization conditions for peptide 4 in a 96-well-plate format using three different Hampton Research crystallization kits (Crystal Screen, Index, and PEG/Ion) with three ratios of peptide and mother liquor per condition (864 experiments).	RESULTS
0	9	Peptide 4	mutant	Peptide 4 afforded crystals in a single set of conditions containing HEPES buffer and Jeffamine M-600—the same crystallization conditions that afforded crystals of peptide 1.	RESULTS
19	27	crystals	evidence	Peptide 4 afforded crystals in a single set of conditions containing HEPES buffer and Jeffamine M-600—the same crystallization conditions that afforded crystals of peptide 1.	RESULTS
86	101	Jeffamine M-600	chemical	Peptide 4 afforded crystals in a single set of conditions containing HEPES buffer and Jeffamine M-600—the same crystallization conditions that afforded crystals of peptide 1.	RESULTS
152	160	crystals	evidence	Peptide 4 afforded crystals in a single set of conditions containing HEPES buffer and Jeffamine M-600—the same crystallization conditions that afforded crystals of peptide 1.	RESULTS
164	173	peptide 1	mutant	Peptide 4 afforded crystals in a single set of conditions containing HEPES buffer and Jeffamine M-600—the same crystallization conditions that afforded crystals of peptide 1.	RESULTS
0	9	Peptide 2	mutant	Peptide 2 also afforded crystals in these conditions.	RESULTS
24	32	crystals	evidence	Peptide 2 also afforded crystals in these conditions.	RESULTS
63	71	crystals	evidence	We further optimized these conditions to rapidly (∼72 h) yield crystals suitable for X-ray crystallography.	RESULTS
85	106	X-ray crystallography	experimental_method	We further optimized these conditions to rapidly (∼72 h) yield crystals suitable for X-ray crystallography.	RESULTS
42	47	HEPES	chemical	The optimized conditions consist of 0.1 M HEPES at pH 6.4 with 31% Jeffamine M-600 for peptide 4 and 0.1 M HEPES pH 7.1 with 29% Jeffamine M-600 for peptide 2.	RESULTS
67	82	Jeffamine M-600	chemical	The optimized conditions consist of 0.1 M HEPES at pH 6.4 with 31% Jeffamine M-600 for peptide 4 and 0.1 M HEPES pH 7.1 with 29% Jeffamine M-600 for peptide 2.	RESULTS
87	96	peptide 4	mutant	The optimized conditions consist of 0.1 M HEPES at pH 6.4 with 31% Jeffamine M-600 for peptide 4 and 0.1 M HEPES pH 7.1 with 29% Jeffamine M-600 for peptide 2.	RESULTS
107	112	HEPES	chemical	The optimized conditions consist of 0.1 M HEPES at pH 6.4 with 31% Jeffamine M-600 for peptide 4 and 0.1 M HEPES pH 7.1 with 29% Jeffamine M-600 for peptide 2.	RESULTS
129	144	Jeffamine M-600	chemical	The optimized conditions consist of 0.1 M HEPES at pH 6.4 with 31% Jeffamine M-600 for peptide 4 and 0.1 M HEPES pH 7.1 with 29% Jeffamine M-600 for peptide 2.	RESULTS
149	158	peptide 2	mutant	The optimized conditions consist of 0.1 M HEPES at pH 6.4 with 31% Jeffamine M-600 for peptide 4 and 0.1 M HEPES pH 7.1 with 29% Jeffamine M-600 for peptide 2.	RESULTS
0	24	Crystal diffraction data	evidence	Crystal diffraction data for peptides 4 and 2 were collected in-house with a Rigaku MicroMax 007HF X-ray diffractometer at 1.54 Å wavelength.	RESULTS
29	45	peptides 4 and 2	mutant	Crystal diffraction data for peptides 4 and 2 were collected in-house with a Rigaku MicroMax 007HF X-ray diffractometer at 1.54 Å wavelength.	RESULTS
0	24	Crystal diffraction data	evidence	Crystal diffraction data for peptide 2 were also collected at the Advanced Light Source at Lawrence Berkeley National Laboratory with a synchrotron source at 1.00 Å wavelength to achieve higher resolution.	RESULTS
29	38	peptide 2	mutant	Crystal diffraction data for peptide 2 were also collected at the Advanced Light Source at Lawrence Berkeley National Laboratory with a synchrotron source at 1.00 Å wavelength to achieve higher resolution.	RESULTS
10	26	peptides 4 and 2	mutant	Data from peptides 4 and 2 suitable for refinement at 2.30 Å were obtained from the diffractometer; data from peptide 2 suitable for refinement at 1.90 Å were obtained from the synchrotron.	RESULTS
110	119	peptide 2	mutant	Data from peptides 4 and 2 suitable for refinement at 2.30 Å were obtained from the diffractometer; data from peptide 2 suitable for refinement at 1.90 Å were obtained from the synchrotron.	RESULTS
9	25	peptides 4 and 2	mutant	Data for peptides 4 and 2 were scaled and merged using XDS.	RESULTS
0	6	Phases	evidence	Phases for peptide 4 were determined by single-wavelength anomalous diffraction (SAD) phasing by using the coordinates of the iodine anomalous signal from p-iodophenylalanine.	RESULTS
11	20	peptide 4	mutant	Phases for peptide 4 were determined by single-wavelength anomalous diffraction (SAD) phasing by using the coordinates of the iodine anomalous signal from p-iodophenylalanine.	RESULTS
40	79	single-wavelength anomalous diffraction	experimental_method	Phases for peptide 4 were determined by single-wavelength anomalous diffraction (SAD) phasing by using the coordinates of the iodine anomalous signal from p-iodophenylalanine.	RESULTS
81	84	SAD	experimental_method	Phases for peptide 4 were determined by single-wavelength anomalous diffraction (SAD) phasing by using the coordinates of the iodine anomalous signal from p-iodophenylalanine.	RESULTS
86	93	phasing	experimental_method	Phases for peptide 4 were determined by single-wavelength anomalous diffraction (SAD) phasing by using the coordinates of the iodine anomalous signal from p-iodophenylalanine.	RESULTS
126	149	iodine anomalous signal	evidence	Phases for peptide 4 were determined by single-wavelength anomalous diffraction (SAD) phasing by using the coordinates of the iodine anomalous signal from p-iodophenylalanine.	RESULTS
155	174	p-iodophenylalanine	chemical	Phases for peptide 4 were determined by single-wavelength anomalous diffraction (SAD) phasing by using the coordinates of the iodine anomalous signal from p-iodophenylalanine.	RESULTS
0	6	Phases	evidence	Phases for peptide 2 were determined by isomorphous replacement of peptide 4.	RESULTS
11	20	peptide 2	mutant	Phases for peptide 2 were determined by isomorphous replacement of peptide 4.	RESULTS
40	63	isomorphous replacement	experimental_method	Phases for peptide 2 were determined by isomorphous replacement of peptide 4.	RESULTS
67	76	peptide 4	mutant	Phases for peptide 2 were determined by isomorphous replacement of peptide 4.	RESULTS
4	14	structures	evidence	The structures of peptides 2 and 4 were solved and refined in the P6122 space group.	RESULTS
18	34	peptides 2 and 4	mutant	The structures of peptides 2 and 4 were solved and refined in the P6122 space group.	RESULTS
40	46	solved	experimental_method	The structures of peptides 2 and 4 were solved and refined in the P6122 space group.	RESULTS
28	35	peptide	chemical	The asymmetric unit of each peptide consists of six monomers, arranged as two trimers.	RESULTS
52	60	monomers	oligomeric_state	The asymmetric unit of each peptide consists of six monomers, arranged as two trimers.	RESULTS
78	85	trimers	oligomeric_state	The asymmetric unit of each peptide consists of six monomers, arranged as two trimers.	RESULTS
0	16	Peptides 2 and 4	mutant	Peptides 2 and 4 form morphologically identical structures and assemblies in the crystal lattice.	RESULTS
81	96	crystal lattice	evidence	Peptides 2 and 4 form morphologically identical structures and assemblies in the crystal lattice.	RESULTS
0	32	X-ray Crystallographic Structure	evidence	X-ray Crystallographic Structure of Peptide 2 and the Oligomers It Forms	RESULTS
36	45	Peptide 2	mutant	X-ray Crystallographic Structure of Peptide 2 and the Oligomers It Forms	RESULTS
54	63	Oligomers	oligomeric_state	X-ray Crystallographic Structure of Peptide 2 and the Oligomers It Forms	RESULTS
4	36	X-ray crystallographic structure	evidence	The X-ray crystallographic structure of peptide 2 reveals that it folds to form a twisted β-hairpin comprising two β-strands connected by a loop (Figure 2A).	RESULTS
40	49	peptide 2	mutant	The X-ray crystallographic structure of peptide 2 reveals that it folds to form a twisted β-hairpin comprising two β-strands connected by a loop (Figure 2A).	RESULTS
82	99	twisted β-hairpin	structure_element	The X-ray crystallographic structure of peptide 2 reveals that it folds to form a twisted β-hairpin comprising two β-strands connected by a loop (Figure 2A).	RESULTS
115	124	β-strands	structure_element	The X-ray crystallographic structure of peptide 2 reveals that it folds to form a twisted β-hairpin comprising two β-strands connected by a loop (Figure 2A).	RESULTS
140	144	loop	structure_element	The X-ray crystallographic structure of peptide 2 reveals that it folds to form a twisted β-hairpin comprising two β-strands connected by a loop (Figure 2A).	RESULTS
43	52	β-hairpin	structure_element	Eight residues make up each surface of the β-hairpin: L17, F19, A21, D23, A30, I32, L34, and V36 make up one surface; V18, F20, E22, C24, C29, I31, G33, and M35 make up the other surface.	RESULTS
54	57	L17	residue_name_number	Eight residues make up each surface of the β-hairpin: L17, F19, A21, D23, A30, I32, L34, and V36 make up one surface; V18, F20, E22, C24, C29, I31, G33, and M35 make up the other surface.	RESULTS
59	62	F19	residue_name_number	Eight residues make up each surface of the β-hairpin: L17, F19, A21, D23, A30, I32, L34, and V36 make up one surface; V18, F20, E22, C24, C29, I31, G33, and M35 make up the other surface.	RESULTS
64	67	A21	residue_name_number	Eight residues make up each surface of the β-hairpin: L17, F19, A21, D23, A30, I32, L34, and V36 make up one surface; V18, F20, E22, C24, C29, I31, G33, and M35 make up the other surface.	RESULTS
69	72	D23	residue_name_number	Eight residues make up each surface of the β-hairpin: L17, F19, A21, D23, A30, I32, L34, and V36 make up one surface; V18, F20, E22, C24, C29, I31, G33, and M35 make up the other surface.	RESULTS
74	77	A30	residue_name_number	Eight residues make up each surface of the β-hairpin: L17, F19, A21, D23, A30, I32, L34, and V36 make up one surface; V18, F20, E22, C24, C29, I31, G33, and M35 make up the other surface.	RESULTS
79	82	I32	residue_name_number	Eight residues make up each surface of the β-hairpin: L17, F19, A21, D23, A30, I32, L34, and V36 make up one surface; V18, F20, E22, C24, C29, I31, G33, and M35 make up the other surface.	RESULTS
84	87	L34	residue_name_number	Eight residues make up each surface of the β-hairpin: L17, F19, A21, D23, A30, I32, L34, and V36 make up one surface; V18, F20, E22, C24, C29, I31, G33, and M35 make up the other surface.	RESULTS
93	96	V36	residue_name_number	Eight residues make up each surface of the β-hairpin: L17, F19, A21, D23, A30, I32, L34, and V36 make up one surface; V18, F20, E22, C24, C29, I31, G33, and M35 make up the other surface.	RESULTS
118	121	V18	residue_name_number	Eight residues make up each surface of the β-hairpin: L17, F19, A21, D23, A30, I32, L34, and V36 make up one surface; V18, F20, E22, C24, C29, I31, G33, and M35 make up the other surface.	RESULTS
123	126	F20	residue_name_number	Eight residues make up each surface of the β-hairpin: L17, F19, A21, D23, A30, I32, L34, and V36 make up one surface; V18, F20, E22, C24, C29, I31, G33, and M35 make up the other surface.	RESULTS
128	131	E22	residue_name_number	Eight residues make up each surface of the β-hairpin: L17, F19, A21, D23, A30, I32, L34, and V36 make up one surface; V18, F20, E22, C24, C29, I31, G33, and M35 make up the other surface.	RESULTS
133	136	C24	residue_name_number	Eight residues make up each surface of the β-hairpin: L17, F19, A21, D23, A30, I32, L34, and V36 make up one surface; V18, F20, E22, C24, C29, I31, G33, and M35 make up the other surface.	RESULTS
138	141	C29	residue_name_number	Eight residues make up each surface of the β-hairpin: L17, F19, A21, D23, A30, I32, L34, and V36 make up one surface; V18, F20, E22, C24, C29, I31, G33, and M35 make up the other surface.	RESULTS
143	146	I31	residue_name_number	Eight residues make up each surface of the β-hairpin: L17, F19, A21, D23, A30, I32, L34, and V36 make up one surface; V18, F20, E22, C24, C29, I31, G33, and M35 make up the other surface.	RESULTS
148	151	G33	residue_name_number	Eight residues make up each surface of the β-hairpin: L17, F19, A21, D23, A30, I32, L34, and V36 make up one surface; V18, F20, E22, C24, C29, I31, G33, and M35 make up the other surface.	RESULTS
157	160	M35	residue_name_number	Eight residues make up each surface of the β-hairpin: L17, F19, A21, D23, A30, I32, L34, and V36 make up one surface; V18, F20, E22, C24, C29, I31, G33, and M35 make up the other surface.	RESULTS
4	13	β-strands	structure_element	The β-strands of the monomers in the asymmetric unit are virtually identical, differing primarily in rotamers of F20, E22, C24, C29, I31, and M35 (Figure S1).	RESULTS
21	29	monomers	oligomeric_state	The β-strands of the monomers in the asymmetric unit are virtually identical, differing primarily in rotamers of F20, E22, C24, C29, I31, and M35 (Figure S1).	RESULTS
113	116	F20	residue_name_number	The β-strands of the monomers in the asymmetric unit are virtually identical, differing primarily in rotamers of F20, E22, C24, C29, I31, and M35 (Figure S1).	RESULTS
118	121	E22	residue_name_number	The β-strands of the monomers in the asymmetric unit are virtually identical, differing primarily in rotamers of F20, E22, C24, C29, I31, and M35 (Figure S1).	RESULTS
123	126	C24	residue_name_number	The β-strands of the monomers in the asymmetric unit are virtually identical, differing primarily in rotamers of F20, E22, C24, C29, I31, and M35 (Figure S1).	RESULTS
128	131	C29	residue_name_number	The β-strands of the monomers in the asymmetric unit are virtually identical, differing primarily in rotamers of F20, E22, C24, C29, I31, and M35 (Figure S1).	RESULTS
133	136	I31	residue_name_number	The β-strands of the monomers in the asymmetric unit are virtually identical, differing primarily in rotamers of F20, E22, C24, C29, I31, and M35 (Figure S1).	RESULTS
142	145	M35	residue_name_number	The β-strands of the monomers in the asymmetric unit are virtually identical, differing primarily in rotamers of F20, E22, C24, C29, I31, and M35 (Figure S1).	RESULTS
4	22	disulfide linkages	ptm	The disulfide linkages suffered radiation damage under synchrotron radiation.	RESULTS
3	10	refined	experimental_method	We refined three of the β-hairpins with intact disulfide linkages and three with thiols to represent cleaved disulfide linkages in the synchrotron data set (PDB 5HOX).	RESULTS
24	34	β-hairpins	structure_element	We refined three of the β-hairpins with intact disulfide linkages and three with thiols to represent cleaved disulfide linkages in the synchrotron data set (PDB 5HOX).	RESULTS
40	46	intact	protein_state	We refined three of the β-hairpins with intact disulfide linkages and three with thiols to represent cleaved disulfide linkages in the synchrotron data set (PDB 5HOX).	RESULTS
47	65	disulfide linkages	ptm	We refined three of the β-hairpins with intact disulfide linkages and three with thiols to represent cleaved disulfide linkages in the synchrotron data set (PDB 5HOX).	RESULTS
101	108	cleaved	protein_state	We refined three of the β-hairpins with intact disulfide linkages and three with thiols to represent cleaved disulfide linkages in the synchrotron data set (PDB 5HOX).	RESULTS
109	127	disulfide linkages	ptm	We refined three of the β-hairpins with intact disulfide linkages and three with thiols to represent cleaved disulfide linkages in the synchrotron data set (PDB 5HOX).	RESULTS
32	42	disulfides	ptm	No evidence for cleavage of the disulfides was observed in the refinement of the data set collected on the X-ray diffractometer, and we refined all disulfide linkages as intact (PDB 5HOY).	RESULTS
63	73	refinement	experimental_method	No evidence for cleavage of the disulfides was observed in the refinement of the data set collected on the X-ray diffractometer, and we refined all disulfide linkages as intact (PDB 5HOY).	RESULTS
136	143	refined	experimental_method	No evidence for cleavage of the disulfides was observed in the refinement of the data set collected on the X-ray diffractometer, and we refined all disulfide linkages as intact (PDB 5HOY).	RESULTS
148	166	disulfide linkages	ptm	No evidence for cleavage of the disulfides was observed in the refinement of the data set collected on the X-ray diffractometer, and we refined all disulfide linkages as intact (PDB 5HOY).	RESULTS
170	176	intact	protein_state	No evidence for cleavage of the disulfides was observed in the refinement of the data set collected on the X-ray diffractometer, and we refined all disulfide linkages as intact (PDB 5HOY).	RESULTS
36	45	peptide 2	mutant	X-ray crystallographic structure of peptide 2 (PDB 5HOX, synchrotron data set). (A) X-ray crystallographic structure of a representative β-hairpin monomer formed by peptide 2. (B) Overlay of the six β-hairpin monomers in the asymmetric unit.	FIG
84	116	X-ray crystallographic structure	evidence	X-ray crystallographic structure of peptide 2 (PDB 5HOX, synchrotron data set). (A) X-ray crystallographic structure of a representative β-hairpin monomer formed by peptide 2. (B) Overlay of the six β-hairpin monomers in the asymmetric unit.	FIG
137	146	β-hairpin	structure_element	X-ray crystallographic structure of peptide 2 (PDB 5HOX, synchrotron data set). (A) X-ray crystallographic structure of a representative β-hairpin monomer formed by peptide 2. (B) Overlay of the six β-hairpin monomers in the asymmetric unit.	FIG
147	154	monomer	oligomeric_state	X-ray crystallographic structure of peptide 2 (PDB 5HOX, synchrotron data set). (A) X-ray crystallographic structure of a representative β-hairpin monomer formed by peptide 2. (B) Overlay of the six β-hairpin monomers in the asymmetric unit.	FIG
165	174	peptide 2	mutant	X-ray crystallographic structure of peptide 2 (PDB 5HOX, synchrotron data set). (A) X-ray crystallographic structure of a representative β-hairpin monomer formed by peptide 2. (B) Overlay of the six β-hairpin monomers in the asymmetric unit.	FIG
180	187	Overlay	experimental_method	X-ray crystallographic structure of peptide 2 (PDB 5HOX, synchrotron data set). (A) X-ray crystallographic structure of a representative β-hairpin monomer formed by peptide 2. (B) Overlay of the six β-hairpin monomers in the asymmetric unit.	FIG
199	208	β-hairpin	structure_element	X-ray crystallographic structure of peptide 2 (PDB 5HOX, synchrotron data set). (A) X-ray crystallographic structure of a representative β-hairpin monomer formed by peptide 2. (B) Overlay of the six β-hairpin monomers in the asymmetric unit.	FIG
209	217	monomers	oligomeric_state	X-ray crystallographic structure of peptide 2 (PDB 5HOX, synchrotron data set). (A) X-ray crystallographic structure of a representative β-hairpin monomer formed by peptide 2. (B) Overlay of the six β-hairpin monomers in the asymmetric unit.	FIG
4	14	β-hairpins	structure_element	The β-hairpins are shown as cartoons to illustrate the differences in the Aβ25–28 loops.	FIG
74	76	Aβ	protein	The β-hairpins are shown as cartoons to illustrate the differences in the Aβ25–28 loops.	FIG
76	81	25–28	residue_range	The β-hairpins are shown as cartoons to illustrate the differences in the Aβ25–28 loops.	FIG
82	87	loops	structure_element	The β-hairpins are shown as cartoons to illustrate the differences in the Aβ25–28 loops.	FIG
4	6	Aβ	protein	The Aβ25–28 loops of the six monomers within the asymmetric unit vary substantially in backbone geometry and side chain rotamers (Figures 2B and S1).	RESULTS
6	11	25–28	residue_range	The Aβ25–28 loops of the six monomers within the asymmetric unit vary substantially in backbone geometry and side chain rotamers (Figures 2B and S1).	RESULTS
12	17	loops	structure_element	The Aβ25–28 loops of the six monomers within the asymmetric unit vary substantially in backbone geometry and side chain rotamers (Figures 2B and S1).	RESULTS
29	37	monomers	oligomeric_state	The Aβ25–28 loops of the six monomers within the asymmetric unit vary substantially in backbone geometry and side chain rotamers (Figures 2B and S1).	RESULTS
4	20	electron density	evidence	The electron density for the loops is weak and diffuse compared to the electron density for the β-strands.	RESULTS
29	34	loops	structure_element	The electron density for the loops is weak and diffuse compared to the electron density for the β-strands.	RESULTS
71	87	electron density	evidence	The electron density for the loops is weak and diffuse compared to the electron density for the β-strands.	RESULTS
96	105	β-strands	structure_element	The electron density for the loops is weak and diffuse compared to the electron density for the β-strands.	RESULTS
4	12	B values	evidence	The B values for the loops are large, indicating that the loops are dynamic and not well ordered.	RESULTS
21	26	loops	structure_element	The B values for the loops are large, indicating that the loops are dynamic and not well ordered.	RESULTS
58	63	loops	structure_element	The B values for the loops are large, indicating that the loops are dynamic and not well ordered.	RESULTS
77	82	loops	structure_element	Thus, the differences in backbone geometry and side chain rotamers among the loops are likely of little significance and should be interpreted with caution.	RESULTS
0	9	Peptide 2	mutant	Peptide 2 assembles into oligomers similar in morphology to those formed by peptide 1.	RESULTS
25	34	oligomers	oligomeric_state	Peptide 2 assembles into oligomers similar in morphology to those formed by peptide 1.	RESULTS
76	85	peptide 1	mutant	Peptide 2 assembles into oligomers similar in morphology to those formed by peptide 1.	RESULTS
5	14	peptide 1	mutant	Like peptide 1, peptide 2 forms a triangular trimer, and four trimers assemble to form a dodecamer.	RESULTS
16	25	peptide 2	mutant	Like peptide 1, peptide 2 forms a triangular trimer, and four trimers assemble to form a dodecamer.	RESULTS
34	44	triangular	protein_state	Like peptide 1, peptide 2 forms a triangular trimer, and four trimers assemble to form a dodecamer.	RESULTS
45	51	trimer	oligomeric_state	Like peptide 1, peptide 2 forms a triangular trimer, and four trimers assemble to form a dodecamer.	RESULTS
62	69	trimers	oligomeric_state	Like peptide 1, peptide 2 forms a triangular trimer, and four trimers assemble to form a dodecamer.	RESULTS
89	98	dodecamer	oligomeric_state	Like peptide 1, peptide 2 forms a triangular trimer, and four trimers assemble to form a dodecamer.	RESULTS
36	46	dodecamers	oligomeric_state	In the higher-order assembly of the dodecamers formed by peptide 2 a new structure emerges, not seen in peptide 1, an annular pore consisting of five dodecamers.	RESULTS
57	66	peptide 2	mutant	In the higher-order assembly of the dodecamers formed by peptide 2 a new structure emerges, not seen in peptide 1, an annular pore consisting of five dodecamers.	RESULTS
73	82	structure	evidence	In the higher-order assembly of the dodecamers formed by peptide 2 a new structure emerges, not seen in peptide 1, an annular pore consisting of five dodecamers.	RESULTS
104	113	peptide 1	mutant	In the higher-order assembly of the dodecamers formed by peptide 2 a new structure emerges, not seen in peptide 1, an annular pore consisting of five dodecamers.	RESULTS
118	130	annular pore	site	In the higher-order assembly of the dodecamers formed by peptide 2 a new structure emerges, not seen in peptide 1, an annular pore consisting of five dodecamers.	RESULTS
150	160	dodecamers	oligomeric_state	In the higher-order assembly of the dodecamers formed by peptide 2 a new structure emerges, not seen in peptide 1, an annular pore consisting of five dodecamers.	RESULTS
0	6	Trimer	oligomeric_state	Trimer	RESULTS
0	9	Peptide 2	mutant	Peptide 2 forms a trimer, much like that which we observed previously for peptide 1, in which three β-hairpins assemble to form an equilateral triangle (Figure 3A).	RESULTS
18	24	trimer	oligomeric_state	Peptide 2 forms a trimer, much like that which we observed previously for peptide 1, in which three β-hairpins assemble to form an equilateral triangle (Figure 3A).	RESULTS
74	83	peptide 1	mutant	Peptide 2 forms a trimer, much like that which we observed previously for peptide 1, in which three β-hairpins assemble to form an equilateral triangle (Figure 3A).	RESULTS
100	110	β-hairpins	structure_element	Peptide 2 forms a trimer, much like that which we observed previously for peptide 1, in which three β-hairpins assemble to form an equilateral triangle (Figure 3A).	RESULTS
131	151	equilateral triangle	structure_element	Peptide 2 forms a trimer, much like that which we observed previously for peptide 1, in which three β-hairpins assemble to form an equilateral triangle (Figure 3A).	RESULTS
4	10	trimer	oligomeric_state	The trimer maintains all of the same stabilizing contacts as those of peptide 1.	RESULTS
70	79	peptide 1	mutant	The trimer maintains all of the same stabilizing contacts as those of peptide 1.	RESULTS
0	16	Hydrogen bonding	bond_interaction	Hydrogen bonding and hydrophobic interactions between residues on the β-strands comprising Aβ17–23 and Aβ30–36 stabilize the core of the trimer.	RESULTS
21	45	hydrophobic interactions	bond_interaction	Hydrogen bonding and hydrophobic interactions between residues on the β-strands comprising Aβ17–23 and Aβ30–36 stabilize the core of the trimer.	RESULTS
70	79	β-strands	structure_element	Hydrogen bonding and hydrophobic interactions between residues on the β-strands comprising Aβ17–23 and Aβ30–36 stabilize the core of the trimer.	RESULTS
91	93	Aβ	protein	Hydrogen bonding and hydrophobic interactions between residues on the β-strands comprising Aβ17–23 and Aβ30–36 stabilize the core of the trimer.	RESULTS
93	98	17–23	residue_range	Hydrogen bonding and hydrophobic interactions between residues on the β-strands comprising Aβ17–23 and Aβ30–36 stabilize the core of the trimer.	RESULTS
103	105	Aβ	protein	Hydrogen bonding and hydrophobic interactions between residues on the β-strands comprising Aβ17–23 and Aβ30–36 stabilize the core of the trimer.	RESULTS
105	110	30–36	residue_range	Hydrogen bonding and hydrophobic interactions between residues on the β-strands comprising Aβ17–23 and Aβ30–36 stabilize the core of the trimer.	RESULTS
125	129	core	structure_element	Hydrogen bonding and hydrophobic interactions between residues on the β-strands comprising Aβ17–23 and Aβ30–36 stabilize the core of the trimer.	RESULTS
137	143	trimer	oligomeric_state	Hydrogen bonding and hydrophobic interactions between residues on the β-strands comprising Aβ17–23 and Aβ30–36 stabilize the core of the trimer.	RESULTS
4	19	disulfide bonds	ptm	The disulfide bonds between residues 24 and 29 are adjacent to the structural core of the trimer and do not make any substantial intermolecular contacts.	RESULTS
37	39	24	residue_number	The disulfide bonds between residues 24 and 29 are adjacent to the structural core of the trimer and do not make any substantial intermolecular contacts.	RESULTS
44	46	29	residue_number	The disulfide bonds between residues 24 and 29 are adjacent to the structural core of the trimer and do not make any substantial intermolecular contacts.	RESULTS
67	82	structural core	structure_element	The disulfide bonds between residues 24 and 29 are adjacent to the structural core of the trimer and do not make any substantial intermolecular contacts.	RESULTS
90	96	trimer	oligomeric_state	The disulfide bonds between residues 24 and 29 are adjacent to the structural core of the trimer and do not make any substantial intermolecular contacts.	RESULTS
34	41	trimers	oligomeric_state	Two crystallographically distinct trimers comprise the peptide portion of the asymmetric unit.	RESULTS
55	62	peptide	chemical	Two crystallographically distinct trimers comprise the peptide portion of the asymmetric unit.	RESULTS
8	15	trimers	oligomeric_state	The two trimers are almost identical in structure, differing slightly among side chain rotamers and loop conformations.	RESULTS
100	104	loop	structure_element	The two trimers are almost identical in structure, differing slightly among side chain rotamers and loop conformations.	RESULTS
0	32	X-ray crystallographic structure	evidence	X-ray crystallographic structure of the trimer formed by peptide 2. (A) Triangular trimer.	FIG
40	46	trimer	oligomeric_state	X-ray crystallographic structure of the trimer formed by peptide 2. (A) Triangular trimer.	FIG
57	66	peptide 2	mutant	X-ray crystallographic structure of the trimer formed by peptide 2. (A) Triangular trimer.	FIG
72	82	Triangular	protein_state	X-ray crystallographic structure of the trimer formed by peptide 2. (A) Triangular trimer.	FIG
83	89	trimer	oligomeric_state	X-ray crystallographic structure of the trimer formed by peptide 2. (A) Triangular trimer.	FIG
10	15	water	chemical	The three water molecules in the center hole of the trimer are shown as spheres. (B) Detailed view of the intermolecular hydrogen bonds between the main chains of V18 and E22 and δOrn and C24, at the three corners of the triangular trimer. (C) The F19 face of the trimer, with key side chains shown as spheres. (D) The F20 face of the trimer, with key side chains as spheres.	FIG
52	58	trimer	oligomeric_state	The three water molecules in the center hole of the trimer are shown as spheres. (B) Detailed view of the intermolecular hydrogen bonds between the main chains of V18 and E22 and δOrn and C24, at the three corners of the triangular trimer. (C) The F19 face of the trimer, with key side chains shown as spheres. (D) The F20 face of the trimer, with key side chains as spheres.	FIG
121	135	hydrogen bonds	bond_interaction	The three water molecules in the center hole of the trimer are shown as spheres. (B) Detailed view of the intermolecular hydrogen bonds between the main chains of V18 and E22 and δOrn and C24, at the three corners of the triangular trimer. (C) The F19 face of the trimer, with key side chains shown as spheres. (D) The F20 face of the trimer, with key side chains as spheres.	FIG
163	166	V18	residue_name_number	The three water molecules in the center hole of the trimer are shown as spheres. (B) Detailed view of the intermolecular hydrogen bonds between the main chains of V18 and E22 and δOrn and C24, at the three corners of the triangular trimer. (C) The F19 face of the trimer, with key side chains shown as spheres. (D) The F20 face of the trimer, with key side chains as spheres.	FIG
171	174	E22	residue_name_number	The three water molecules in the center hole of the trimer are shown as spheres. (B) Detailed view of the intermolecular hydrogen bonds between the main chains of V18 and E22 and δOrn and C24, at the three corners of the triangular trimer. (C) The F19 face of the trimer, with key side chains shown as spheres. (D) The F20 face of the trimer, with key side chains as spheres.	FIG
179	183	δOrn	structure_element	The three water molecules in the center hole of the trimer are shown as spheres. (B) Detailed view of the intermolecular hydrogen bonds between the main chains of V18 and E22 and δOrn and C24, at the three corners of the triangular trimer. (C) The F19 face of the trimer, with key side chains shown as spheres. (D) The F20 face of the trimer, with key side chains as spheres.	FIG
188	191	C24	residue_name_number	The three water molecules in the center hole of the trimer are shown as spheres. (B) Detailed view of the intermolecular hydrogen bonds between the main chains of V18 and E22 and δOrn and C24, at the three corners of the triangular trimer. (C) The F19 face of the trimer, with key side chains shown as spheres. (D) The F20 face of the trimer, with key side chains as spheres.	FIG
221	231	triangular	protein_state	The three water molecules in the center hole of the trimer are shown as spheres. (B) Detailed view of the intermolecular hydrogen bonds between the main chains of V18 and E22 and δOrn and C24, at the three corners of the triangular trimer. (C) The F19 face of the trimer, with key side chains shown as spheres. (D) The F20 face of the trimer, with key side chains as spheres.	FIG
232	238	trimer	oligomeric_state	The three water molecules in the center hole of the trimer are shown as spheres. (B) Detailed view of the intermolecular hydrogen bonds between the main chains of V18 and E22 and δOrn and C24, at the three corners of the triangular trimer. (C) The F19 face of the trimer, with key side chains shown as spheres. (D) The F20 face of the trimer, with key side chains as spheres.	FIG
248	251	F19	residue_name_number	The three water molecules in the center hole of the trimer are shown as spheres. (B) Detailed view of the intermolecular hydrogen bonds between the main chains of V18 and E22 and δOrn and C24, at the three corners of the triangular trimer. (C) The F19 face of the trimer, with key side chains shown as spheres. (D) The F20 face of the trimer, with key side chains as spheres.	FIG
264	270	trimer	oligomeric_state	The three water molecules in the center hole of the trimer are shown as spheres. (B) Detailed view of the intermolecular hydrogen bonds between the main chains of V18 and E22 and δOrn and C24, at the three corners of the triangular trimer. (C) The F19 face of the trimer, with key side chains shown as spheres. (D) The F20 face of the trimer, with key side chains as spheres.	FIG
319	322	F20	residue_name_number	The three water molecules in the center hole of the trimer are shown as spheres. (B) Detailed view of the intermolecular hydrogen bonds between the main chains of V18 and E22 and δOrn and C24, at the three corners of the triangular trimer. (C) The F19 face of the trimer, with key side chains shown as spheres. (D) The F20 face of the trimer, with key side chains as spheres.	FIG
335	341	trimer	oligomeric_state	The three water molecules in the center hole of the trimer are shown as spheres. (B) Detailed view of the intermolecular hydrogen bonds between the main chains of V18 and E22 and δOrn and C24, at the three corners of the triangular trimer. (C) The F19 face of the trimer, with key side chains shown as spheres. (D) The F20 face of the trimer, with key side chains as spheres.	FIG
31	45	hydrogen bonds	bond_interaction	A network of 18 intermolecular hydrogen bonds helps stabilize the trimer.	RESULTS
66	72	trimer	oligomeric_state	A network of 18 intermolecular hydrogen bonds helps stabilize the trimer.	RESULTS
22	28	trimer	oligomeric_state	At the corners of the trimer, the pairs of β-hairpin monomers form four hydrogen bonds: two between the main chains of V18 and E22 and two between δOrn and the main chain of C24 (Figure 3B).	RESULTS
43	52	β-hairpin	structure_element	At the corners of the trimer, the pairs of β-hairpin monomers form four hydrogen bonds: two between the main chains of V18 and E22 and two between δOrn and the main chain of C24 (Figure 3B).	RESULTS
53	61	monomers	oligomeric_state	At the corners of the trimer, the pairs of β-hairpin monomers form four hydrogen bonds: two between the main chains of V18 and E22 and two between δOrn and the main chain of C24 (Figure 3B).	RESULTS
72	86	hydrogen bonds	bond_interaction	At the corners of the trimer, the pairs of β-hairpin monomers form four hydrogen bonds: two between the main chains of V18 and E22 and two between δOrn and the main chain of C24 (Figure 3B).	RESULTS
119	122	V18	residue_name_number	At the corners of the trimer, the pairs of β-hairpin monomers form four hydrogen bonds: two between the main chains of V18 and E22 and two between δOrn and the main chain of C24 (Figure 3B).	RESULTS
127	130	E22	residue_name_number	At the corners of the trimer, the pairs of β-hairpin monomers form four hydrogen bonds: two between the main chains of V18 and E22 and two between δOrn and the main chain of C24 (Figure 3B).	RESULTS
147	151	δOrn	structure_element	At the corners of the trimer, the pairs of β-hairpin monomers form four hydrogen bonds: two between the main chains of V18 and E22 and two between δOrn and the main chain of C24 (Figure 3B).	RESULTS
174	177	C24	residue_name_number	At the corners of the trimer, the pairs of β-hairpin monomers form four hydrogen bonds: two between the main chains of V18 and E22 and two between δOrn and the main chain of C24 (Figure 3B).	RESULTS
14	19	water	chemical	Three ordered water molecules fill the hole in the center of the trimer, hydrogen bonding to each other and to the main chain of F20 (Figure 3A).	RESULTS
65	71	trimer	oligomeric_state	Three ordered water molecules fill the hole in the center of the trimer, hydrogen bonding to each other and to the main chain of F20 (Figure 3A).	RESULTS
73	89	hydrogen bonding	bond_interaction	Three ordered water molecules fill the hole in the center of the trimer, hydrogen bonding to each other and to the main chain of F20 (Figure 3A).	RESULTS
129	132	F20	residue_name_number	Three ordered water molecules fill the hole in the center of the trimer, hydrogen bonding to each other and to the main chain of F20 (Figure 3A).	RESULTS
0	20	Hydrophobic contacts	bond_interaction	Hydrophobic contacts between residues at the three corners of the trimer, where the β-hairpins meet, further stabilize the trimer.	RESULTS
66	72	trimer	oligomeric_state	Hydrophobic contacts between residues at the three corners of the trimer, where the β-hairpins meet, further stabilize the trimer.	RESULTS
84	94	β-hairpins	structure_element	Hydrophobic contacts between residues at the three corners of the trimer, where the β-hairpins meet, further stabilize the trimer.	RESULTS
123	129	trimer	oligomeric_state	Hydrophobic contacts between residues at the three corners of the trimer, where the β-hairpins meet, further stabilize the trimer.	RESULTS
44	47	L17	residue_name_number	At each corner, the side chains of residues L17, F19, and V36 of one β-hairpin pack against the side chains of residues A21, I32, L34, and also D23 of the adjacent β-hairpin to create a hydrophobic cluster (Figure 3C). The three hydrophobic clusters create a large hydrophobic surface on one face of the trimer.	RESULTS
49	52	F19	residue_name_number	At each corner, the side chains of residues L17, F19, and V36 of one β-hairpin pack against the side chains of residues A21, I32, L34, and also D23 of the adjacent β-hairpin to create a hydrophobic cluster (Figure 3C). The three hydrophobic clusters create a large hydrophobic surface on one face of the trimer.	RESULTS
58	61	V36	residue_name_number	At each corner, the side chains of residues L17, F19, and V36 of one β-hairpin pack against the side chains of residues A21, I32, L34, and also D23 of the adjacent β-hairpin to create a hydrophobic cluster (Figure 3C). The three hydrophobic clusters create a large hydrophobic surface on one face of the trimer.	RESULTS
69	78	β-hairpin	structure_element	At each corner, the side chains of residues L17, F19, and V36 of one β-hairpin pack against the side chains of residues A21, I32, L34, and also D23 of the adjacent β-hairpin to create a hydrophobic cluster (Figure 3C). The three hydrophobic clusters create a large hydrophobic surface on one face of the trimer.	RESULTS
120	123	A21	residue_name_number	At each corner, the side chains of residues L17, F19, and V36 of one β-hairpin pack against the side chains of residues A21, I32, L34, and also D23 of the adjacent β-hairpin to create a hydrophobic cluster (Figure 3C). The three hydrophobic clusters create a large hydrophobic surface on one face of the trimer.	RESULTS
125	128	I32	residue_name_number	At each corner, the side chains of residues L17, F19, and V36 of one β-hairpin pack against the side chains of residues A21, I32, L34, and also D23 of the adjacent β-hairpin to create a hydrophobic cluster (Figure 3C). The three hydrophobic clusters create a large hydrophobic surface on one face of the trimer.	RESULTS
130	133	L34	residue_name_number	At each corner, the side chains of residues L17, F19, and V36 of one β-hairpin pack against the side chains of residues A21, I32, L34, and also D23 of the adjacent β-hairpin to create a hydrophobic cluster (Figure 3C). The three hydrophobic clusters create a large hydrophobic surface on one face of the trimer.	RESULTS
144	147	D23	residue_name_number	At each corner, the side chains of residues L17, F19, and V36 of one β-hairpin pack against the side chains of residues A21, I32, L34, and also D23 of the adjacent β-hairpin to create a hydrophobic cluster (Figure 3C). The three hydrophobic clusters create a large hydrophobic surface on one face of the trimer.	RESULTS
164	173	β-hairpin	structure_element	At each corner, the side chains of residues L17, F19, and V36 of one β-hairpin pack against the side chains of residues A21, I32, L34, and also D23 of the adjacent β-hairpin to create a hydrophobic cluster (Figure 3C). The three hydrophobic clusters create a large hydrophobic surface on one face of the trimer.	RESULTS
186	205	hydrophobic cluster	site	At each corner, the side chains of residues L17, F19, and V36 of one β-hairpin pack against the side chains of residues A21, I32, L34, and also D23 of the adjacent β-hairpin to create a hydrophobic cluster (Figure 3C). The three hydrophobic clusters create a large hydrophobic surface on one face of the trimer.	RESULTS
229	249	hydrophobic clusters	site	At each corner, the side chains of residues L17, F19, and V36 of one β-hairpin pack against the side chains of residues A21, I32, L34, and also D23 of the adjacent β-hairpin to create a hydrophobic cluster (Figure 3C). The three hydrophobic clusters create a large hydrophobic surface on one face of the trimer.	RESULTS
265	284	hydrophobic surface	site	At each corner, the side chains of residues L17, F19, and V36 of one β-hairpin pack against the side chains of residues A21, I32, L34, and also D23 of the adjacent β-hairpin to create a hydrophobic cluster (Figure 3C). The three hydrophobic clusters create a large hydrophobic surface on one face of the trimer.	RESULTS
304	310	trimer	oligomeric_state	At each corner, the side chains of residues L17, F19, and V36 of one β-hairpin pack against the side chains of residues A21, I32, L34, and also D23 of the adjacent β-hairpin to create a hydrophobic cluster (Figure 3C). The three hydrophobic clusters create a large hydrophobic surface on one face of the trimer.	RESULTS
22	28	trimer	oligomeric_state	The other face of the trimer displays a smaller hydrophobic surface, which includes the side chains of residues V18, F20, and I31 of the three β-hairpins (Figure 3D).	RESULTS
48	67	hydrophobic surface	site	The other face of the trimer displays a smaller hydrophobic surface, which includes the side chains of residues V18, F20, and I31 of the three β-hairpins (Figure 3D).	RESULTS
112	115	V18	residue_name_number	The other face of the trimer displays a smaller hydrophobic surface, which includes the side chains of residues V18, F20, and I31 of the three β-hairpins (Figure 3D).	RESULTS
117	120	F20	residue_name_number	The other face of the trimer displays a smaller hydrophobic surface, which includes the side chains of residues V18, F20, and I31 of the three β-hairpins (Figure 3D).	RESULTS
126	129	I31	residue_name_number	The other face of the trimer displays a smaller hydrophobic surface, which includes the side chains of residues V18, F20, and I31 of the three β-hairpins (Figure 3D).	RESULTS
143	153	β-hairpins	structure_element	The other face of the trimer displays a smaller hydrophobic surface, which includes the side chains of residues V18, F20, and I31 of the three β-hairpins (Figure 3D).	RESULTS
63	66	F19	residue_name_number	In subsequent discussion, we designate the former surface the “F19 face” and the latter surface the “F20 face”.	RESULTS
101	104	F20	residue_name_number	In subsequent discussion, we designate the former surface the “F19 face” and the latter surface the “F20 face”.	RESULTS
0	9	Dodecamer	oligomeric_state	Dodecamer	RESULTS
5	12	trimers	oligomeric_state	Four trimers assemble to form a dodecamer.	RESULTS
32	41	dodecamer	oligomeric_state	Four trimers assemble to form a dodecamer.	RESULTS
9	16	trimers	oligomeric_state	The four trimers arrange in a tetrahedral fashion, creating a central cavity inside the dodecamer. Because each trimer is triangular, the resulting arrangement resembles an octahedron.	RESULTS
30	41	tetrahedral	protein_state	The four trimers arrange in a tetrahedral fashion, creating a central cavity inside the dodecamer. Because each trimer is triangular, the resulting arrangement resembles an octahedron.	RESULTS
62	76	central cavity	site	The four trimers arrange in a tetrahedral fashion, creating a central cavity inside the dodecamer. Because each trimer is triangular, the resulting arrangement resembles an octahedron.	RESULTS
88	97	dodecamer	oligomeric_state	The four trimers arrange in a tetrahedral fashion, creating a central cavity inside the dodecamer. Because each trimer is triangular, the resulting arrangement resembles an octahedron.	RESULTS
112	118	trimer	oligomeric_state	The four trimers arrange in a tetrahedral fashion, creating a central cavity inside the dodecamer. Because each trimer is triangular, the resulting arrangement resembles an octahedron.	RESULTS
122	132	triangular	protein_state	The four trimers arrange in a tetrahedral fashion, creating a central cavity inside the dodecamer. Because each trimer is triangular, the resulting arrangement resembles an octahedron.	RESULTS
173	183	octahedron	protein_state	The four trimers arrange in a tetrahedral fashion, creating a central cavity inside the dodecamer. Because each trimer is triangular, the resulting arrangement resembles an octahedron.	RESULTS
15	25	β-hairpins	structure_element	Each of the 12 β-hairpins constitutes an edge of the octahedron, and the triangular trimers occupy four of the eight faces of the octahedron.	RESULTS
53	63	octahedron	protein_state	Each of the 12 β-hairpins constitutes an edge of the octahedron, and the triangular trimers occupy four of the eight faces of the octahedron.	RESULTS
73	83	triangular	protein_state	Each of the 12 β-hairpins constitutes an edge of the octahedron, and the triangular trimers occupy four of the eight faces of the octahedron.	RESULTS
84	91	trimers	oligomeric_state	Each of the 12 β-hairpins constitutes an edge of the octahedron, and the triangular trimers occupy four of the eight faces of the octahedron.	RESULTS
130	140	octahedron	protein_state	Each of the 12 β-hairpins constitutes an edge of the octahedron, and the triangular trimers occupy four of the eight faces of the octahedron.	RESULTS
26	36	octahedral	protein_state	Figure 4A illustrates the octahedral shape of the dodecamer.	RESULTS
50	59	dodecamer	oligomeric_state	Figure 4A illustrates the octahedral shape of the dodecamer.	RESULTS
26	37	tetrahedral	protein_state	Figure 4B illustrates the tetrahedral arrangement of the four trimers.	RESULTS
62	69	trimers	oligomeric_state	Figure 4B illustrates the tetrahedral arrangement of the four trimers.	RESULTS
40	49	dodecamer	oligomeric_state	X-ray crystallographic structure of the dodecamer formed by peptide 2. (A) View of the dodecamer that illustrates the octahedral shape. (B) View of the dodecamer that illustrates the tetrahedral arrangement of the four trimers that comprise the dodecamer. (C) View of two trimer subunits from inside the cavity of the dodecamer.	FIG
60	69	peptide 2	mutant	X-ray crystallographic structure of the dodecamer formed by peptide 2. (A) View of the dodecamer that illustrates the octahedral shape. (B) View of the dodecamer that illustrates the tetrahedral arrangement of the four trimers that comprise the dodecamer. (C) View of two trimer subunits from inside the cavity of the dodecamer.	FIG
87	96	dodecamer	oligomeric_state	X-ray crystallographic structure of the dodecamer formed by peptide 2. (A) View of the dodecamer that illustrates the octahedral shape. (B) View of the dodecamer that illustrates the tetrahedral arrangement of the four trimers that comprise the dodecamer. (C) View of two trimer subunits from inside the cavity of the dodecamer.	FIG
118	128	octahedral	protein_state	X-ray crystallographic structure of the dodecamer formed by peptide 2. (A) View of the dodecamer that illustrates the octahedral shape. (B) View of the dodecamer that illustrates the tetrahedral arrangement of the four trimers that comprise the dodecamer. (C) View of two trimer subunits from inside the cavity of the dodecamer.	FIG
152	161	dodecamer	oligomeric_state	X-ray crystallographic structure of the dodecamer formed by peptide 2. (A) View of the dodecamer that illustrates the octahedral shape. (B) View of the dodecamer that illustrates the tetrahedral arrangement of the four trimers that comprise the dodecamer. (C) View of two trimer subunits from inside the cavity of the dodecamer.	FIG
183	194	tetrahedral	protein_state	X-ray crystallographic structure of the dodecamer formed by peptide 2. (A) View of the dodecamer that illustrates the octahedral shape. (B) View of the dodecamer that illustrates the tetrahedral arrangement of the four trimers that comprise the dodecamer. (C) View of two trimer subunits from inside the cavity of the dodecamer.	FIG
219	226	trimers	oligomeric_state	X-ray crystallographic structure of the dodecamer formed by peptide 2. (A) View of the dodecamer that illustrates the octahedral shape. (B) View of the dodecamer that illustrates the tetrahedral arrangement of the four trimers that comprise the dodecamer. (C) View of two trimer subunits from inside the cavity of the dodecamer.	FIG
245	254	dodecamer	oligomeric_state	X-ray crystallographic structure of the dodecamer formed by peptide 2. (A) View of the dodecamer that illustrates the octahedral shape. (B) View of the dodecamer that illustrates the tetrahedral arrangement of the four trimers that comprise the dodecamer. (C) View of two trimer subunits from inside the cavity of the dodecamer.	FIG
272	278	trimer	oligomeric_state	X-ray crystallographic structure of the dodecamer formed by peptide 2. (A) View of the dodecamer that illustrates the octahedral shape. (B) View of the dodecamer that illustrates the tetrahedral arrangement of the four trimers that comprise the dodecamer. (C) View of two trimer subunits from inside the cavity of the dodecamer.	FIG
279	287	subunits	structure_element	X-ray crystallographic structure of the dodecamer formed by peptide 2. (A) View of the dodecamer that illustrates the octahedral shape. (B) View of the dodecamer that illustrates the tetrahedral arrangement of the four trimers that comprise the dodecamer. (C) View of two trimer subunits from inside the cavity of the dodecamer.	FIG
304	310	cavity	site	X-ray crystallographic structure of the dodecamer formed by peptide 2. (A) View of the dodecamer that illustrates the octahedral shape. (B) View of the dodecamer that illustrates the tetrahedral arrangement of the four trimers that comprise the dodecamer. (C) View of two trimer subunits from inside the cavity of the dodecamer.	FIG
318	327	dodecamer	oligomeric_state	X-ray crystallographic structure of the dodecamer formed by peptide 2. (A) View of the dodecamer that illustrates the octahedral shape. (B) View of the dodecamer that illustrates the tetrahedral arrangement of the four trimers that comprise the dodecamer. (C) View of two trimer subunits from inside the cavity of the dodecamer.	FIG
9	12	L17	residue_name_number	Residues L17, L34, and V36 are shown as spheres, illustrating the hydrophobic packing that occurs at the six vertices of the dodecamer. (D) Detailed view of one of the six vertices of the dodecamer.	FIG
14	17	L34	residue_name_number	Residues L17, L34, and V36 are shown as spheres, illustrating the hydrophobic packing that occurs at the six vertices of the dodecamer. (D) Detailed view of one of the six vertices of the dodecamer.	FIG
23	26	V36	residue_name_number	Residues L17, L34, and V36 are shown as spheres, illustrating the hydrophobic packing that occurs at the six vertices of the dodecamer. (D) Detailed view of one of the six vertices of the dodecamer.	FIG
66	85	hydrophobic packing	bond_interaction	Residues L17, L34, and V36 are shown as spheres, illustrating the hydrophobic packing that occurs at the six vertices of the dodecamer. (D) Detailed view of one of the six vertices of the dodecamer.	FIG
125	134	dodecamer	oligomeric_state	Residues L17, L34, and V36 are shown as spheres, illustrating the hydrophobic packing that occurs at the six vertices of the dodecamer. (D) Detailed view of one of the six vertices of the dodecamer.	FIG
188	197	dodecamer	oligomeric_state	Residues L17, L34, and V36 are shown as spheres, illustrating the hydrophobic packing that occurs at the six vertices of the dodecamer. (D) Detailed view of one of the six vertices of the dodecamer.	FIG
4	7	F19	residue_name_number	The F19 faces of the trimers line the interior of the dodecamer.	RESULTS
21	28	trimers	oligomeric_state	The F19 faces of the trimers line the interior of the dodecamer.	RESULTS
54	63	dodecamer	oligomeric_state	The F19 faces of the trimers line the interior of the dodecamer.	RESULTS
21	40	hydrophobic packing	bond_interaction	At the six vertices, hydrophobic packing between the side chains of L17, L34, and V36 helps stabilize the dodecamer (Figures 4C and D).	RESULTS
68	71	L17	residue_name_number	At the six vertices, hydrophobic packing between the side chains of L17, L34, and V36 helps stabilize the dodecamer (Figures 4C and D).	RESULTS
73	76	L34	residue_name_number	At the six vertices, hydrophobic packing between the side chains of L17, L34, and V36 helps stabilize the dodecamer (Figures 4C and D).	RESULTS
82	85	V36	residue_name_number	At the six vertices, hydrophobic packing between the side chains of L17, L34, and V36 helps stabilize the dodecamer (Figures 4C and D).	RESULTS
106	115	dodecamer	oligomeric_state	At the six vertices, hydrophobic packing between the side chains of L17, L34, and V36 helps stabilize the dodecamer (Figures 4C and D).	RESULTS
40	43	D23	residue_name_number	Salt bridges between the side chains of D23 and δOrn at the vertices further stabilize the dodecamer.	RESULTS
48	52	δOrn	structure_element	Salt bridges between the side chains of D23 and δOrn at the vertices further stabilize the dodecamer.	RESULTS
91	100	dodecamer	oligomeric_state	Salt bridges between the side chains of D23 and δOrn at the vertices further stabilize the dodecamer.	RESULTS
38	40	Aβ	protein	Each of the six vertices includes two Aβ25–28 loops that extend past the core of the dodecamer without making any substantial intermolecular contacts.	RESULTS
40	45	25–28	residue_range	Each of the six vertices includes two Aβ25–28 loops that extend past the core of the dodecamer without making any substantial intermolecular contacts.	RESULTS
46	51	loops	structure_element	Each of the six vertices includes two Aβ25–28 loops that extend past the core of the dodecamer without making any substantial intermolecular contacts.	RESULTS
73	77	core	structure_element	Each of the six vertices includes two Aβ25–28 loops that extend past the core of the dodecamer without making any substantial intermolecular contacts.	RESULTS
85	94	dodecamer	oligomeric_state	Each of the six vertices includes two Aβ25–28 loops that extend past the core of the dodecamer without making any substantial intermolecular contacts.	RESULTS
20	29	dodecamer	oligomeric_state	The exterior of the dodecamer displays four F20 faces (Figure S3).	RESULTS
44	47	F20	residue_name_number	The exterior of the dodecamer displays four F20 faces (Figure S3).	RESULTS
7	22	crystal lattice	evidence	In the crystal lattice, each F20 face of one dodecamer packs against an F20 face of another dodecamer.	RESULTS
29	32	F20	residue_name_number	In the crystal lattice, each F20 face of one dodecamer packs against an F20 face of another dodecamer.	RESULTS
45	54	dodecamer	oligomeric_state	In the crystal lattice, each F20 face of one dodecamer packs against an F20 face of another dodecamer.	RESULTS
72	75	F20	residue_name_number	In the crystal lattice, each F20 face of one dodecamer packs against an F20 face of another dodecamer.	RESULTS
92	101	dodecamer	oligomeric_state	In the crystal lattice, each F20 face of one dodecamer packs against an F20 face of another dodecamer.	RESULTS
46	55	dodecamer	oligomeric_state	Although the asymmetric unit comprises half a dodecamer, the crystal lattice may be thought of as being built of dodecamers.	RESULTS
61	76	crystal lattice	evidence	Although the asymmetric unit comprises half a dodecamer, the crystal lattice may be thought of as being built of dodecamers.	RESULTS
113	123	dodecamers	oligomeric_state	Although the asymmetric unit comprises half a dodecamer, the crystal lattice may be thought of as being built of dodecamers.	RESULTS
4	24	electron density map	evidence	The electron density map for the X-ray crystallographic structure of peptide 2 has long tubes of electron density inside the central cavity of the dodecamer.	RESULTS
33	65	X-ray crystallographic structure	evidence	The electron density map for the X-ray crystallographic structure of peptide 2 has long tubes of electron density inside the central cavity of the dodecamer.	RESULTS
69	78	peptide 2	mutant	The electron density map for the X-ray crystallographic structure of peptide 2 has long tubes of electron density inside the central cavity of the dodecamer.	RESULTS
97	113	electron density	evidence	The electron density map for the X-ray crystallographic structure of peptide 2 has long tubes of electron density inside the central cavity of the dodecamer.	RESULTS
125	139	central cavity	site	The electron density map for the X-ray crystallographic structure of peptide 2 has long tubes of electron density inside the central cavity of the dodecamer.	RESULTS
147	156	dodecamer	oligomeric_state	The electron density map for the X-ray crystallographic structure of peptide 2 has long tubes of electron density inside the central cavity of the dodecamer.	RESULTS
28	44	electron density	evidence	The shape and length of the electron density is consistent with the structure of Jeffamine M-600, which is an essential component of the crystallization conditions.	RESULTS
68	77	structure	evidence	The shape and length of the electron density is consistent with the structure of Jeffamine M-600, which is an essential component of the crystallization conditions.	RESULTS
81	96	Jeffamine M-600	chemical	The shape and length of the electron density is consistent with the structure of Jeffamine M-600, which is an essential component of the crystallization conditions.	RESULTS
0	15	Jeffamine M-600	chemical	Jeffamine M-600 is a polypropylene glycol derivative with a 2-methoxyethoxy unit at one end and a 2-aminopropyl unit at the other end.	RESULTS
9	24	Jeffamine M-600	chemical	Although Jeffamine M-600 is a heterogeneous mixture with varying chain lengths and stereochemistry, we modeled a single stereoisomer with nine propylene glycol units (n = 9) to fit the electron density.	RESULTS
185	201	electron density	evidence	Although Jeffamine M-600 is a heterogeneous mixture with varying chain lengths and stereochemistry, we modeled a single stereoisomer with nine propylene glycol units (n = 9) to fit the electron density.	RESULTS
4	19	Jeffamine M-600	chemical	The Jeffamine M-600 appears to stabilize the dodecamer by occupying the central cavity and making hydrophobic contacts with residues lining the cavity (Figure S3).	RESULTS
45	54	dodecamer	oligomeric_state	The Jeffamine M-600 appears to stabilize the dodecamer by occupying the central cavity and making hydrophobic contacts with residues lining the cavity (Figure S3).	RESULTS
72	86	central cavity	site	The Jeffamine M-600 appears to stabilize the dodecamer by occupying the central cavity and making hydrophobic contacts with residues lining the cavity (Figure S3).	RESULTS
98	118	hydrophobic contacts	bond_interaction	The Jeffamine M-600 appears to stabilize the dodecamer by occupying the central cavity and making hydrophobic contacts with residues lining the cavity (Figure S3).	RESULTS
144	150	cavity	site	The Jeffamine M-600 appears to stabilize the dodecamer by occupying the central cavity and making hydrophobic contacts with residues lining the cavity (Figure S3).	RESULTS
5	14	dodecamer	oligomeric_state	In a dodecamer formed by full-length Aβ, the hydrophobic C-terminal residues (Aβ37–40 or Aβ37–42) might play a similar role in filling the dodecamer and thus create a packed hydrophobic core within the central cavity of the dodecamer.	RESULTS
25	36	full-length	protein_state	In a dodecamer formed by full-length Aβ, the hydrophobic C-terminal residues (Aβ37–40 or Aβ37–42) might play a similar role in filling the dodecamer and thus create a packed hydrophobic core within the central cavity of the dodecamer.	RESULTS
37	39	Aβ	protein	In a dodecamer formed by full-length Aβ, the hydrophobic C-terminal residues (Aβ37–40 or Aβ37–42) might play a similar role in filling the dodecamer and thus create a packed hydrophobic core within the central cavity of the dodecamer.	RESULTS
78	80	Aβ	protein	In a dodecamer formed by full-length Aβ, the hydrophobic C-terminal residues (Aβ37–40 or Aβ37–42) might play a similar role in filling the dodecamer and thus create a packed hydrophobic core within the central cavity of the dodecamer.	RESULTS
80	85	37–40	residue_range	In a dodecamer formed by full-length Aβ, the hydrophobic C-terminal residues (Aβ37–40 or Aβ37–42) might play a similar role in filling the dodecamer and thus create a packed hydrophobic core within the central cavity of the dodecamer.	RESULTS
89	91	Aβ	protein	In a dodecamer formed by full-length Aβ, the hydrophobic C-terminal residues (Aβ37–40 or Aβ37–42) might play a similar role in filling the dodecamer and thus create a packed hydrophobic core within the central cavity of the dodecamer.	RESULTS
91	96	37–42	residue_range	In a dodecamer formed by full-length Aβ, the hydrophobic C-terminal residues (Aβ37–40 or Aβ37–42) might play a similar role in filling the dodecamer and thus create a packed hydrophobic core within the central cavity of the dodecamer.	RESULTS
139	148	dodecamer	oligomeric_state	In a dodecamer formed by full-length Aβ, the hydrophobic C-terminal residues (Aβ37–40 or Aβ37–42) might play a similar role in filling the dodecamer and thus create a packed hydrophobic core within the central cavity of the dodecamer.	RESULTS
174	190	hydrophobic core	site	In a dodecamer formed by full-length Aβ, the hydrophobic C-terminal residues (Aβ37–40 or Aβ37–42) might play a similar role in filling the dodecamer and thus create a packed hydrophobic core within the central cavity of the dodecamer.	RESULTS
202	216	central cavity	site	In a dodecamer formed by full-length Aβ, the hydrophobic C-terminal residues (Aβ37–40 or Aβ37–42) might play a similar role in filling the dodecamer and thus create a packed hydrophobic core within the central cavity of the dodecamer.	RESULTS
224	233	dodecamer	oligomeric_state	In a dodecamer formed by full-length Aβ, the hydrophobic C-terminal residues (Aβ37–40 or Aβ37–42) might play a similar role in filling the dodecamer and thus create a packed hydrophobic core within the central cavity of the dodecamer.	RESULTS
0	12	Annular Pore	site	Annular Pore	RESULTS
5	15	dodecamers	oligomeric_state	Five dodecamers assemble to form an annular porelike structure (Figure 5A).	RESULTS
44	52	porelike	structure_element	Five dodecamers assemble to form an annular porelike structure (Figure 5A).	RESULTS
0	19	Hydrophobic packing	bond_interaction	Hydrophobic packing between the F20 faces of trimers displayed on the outer surface of each dodecamer stabilizes the porelike assembly.	RESULTS
32	35	F20	residue_name_number	Hydrophobic packing between the F20 faces of trimers displayed on the outer surface of each dodecamer stabilizes the porelike assembly.	RESULTS
45	52	trimers	oligomeric_state	Hydrophobic packing between the F20 faces of trimers displayed on the outer surface of each dodecamer stabilizes the porelike assembly.	RESULTS
92	101	dodecamer	oligomeric_state	Hydrophobic packing between the F20 faces of trimers displayed on the outer surface of each dodecamer stabilizes the porelike assembly.	RESULTS
50	57	trimers	oligomeric_state	Two morphologically distinct interactions between trimers occur at the interfaces of the five dodecamers: one in which the trimers are eclipsed (Figure 5B), and one in which the trimers are staggered (Figure 5C).	RESULTS
71	81	interfaces	site	Two morphologically distinct interactions between trimers occur at the interfaces of the five dodecamers: one in which the trimers are eclipsed (Figure 5B), and one in which the trimers are staggered (Figure 5C).	RESULTS
94	104	dodecamers	oligomeric_state	Two morphologically distinct interactions between trimers occur at the interfaces of the five dodecamers: one in which the trimers are eclipsed (Figure 5B), and one in which the trimers are staggered (Figure 5C).	RESULTS
123	130	trimers	oligomeric_state	Two morphologically distinct interactions between trimers occur at the interfaces of the five dodecamers: one in which the trimers are eclipsed (Figure 5B), and one in which the trimers are staggered (Figure 5C).	RESULTS
135	143	eclipsed	protein_state	Two morphologically distinct interactions between trimers occur at the interfaces of the five dodecamers: one in which the trimers are eclipsed (Figure 5B), and one in which the trimers are staggered (Figure 5C).	RESULTS
178	185	trimers	oligomeric_state	Two morphologically distinct interactions between trimers occur at the interfaces of the five dodecamers: one in which the trimers are eclipsed (Figure 5B), and one in which the trimers are staggered (Figure 5C).	RESULTS
190	199	staggered	protein_state	Two morphologically distinct interactions between trimers occur at the interfaces of the five dodecamers: one in which the trimers are eclipsed (Figure 5B), and one in which the trimers are staggered (Figure 5C).	RESULTS
0	19	Hydrophobic packing	bond_interaction	Hydrophobic packing between the side chains of F20, I31, and E22 stabilizes these interfaces (Figure 5D and E).	RESULTS
47	50	F20	residue_name_number	Hydrophobic packing between the side chains of F20, I31, and E22 stabilizes these interfaces (Figure 5D and E).	RESULTS
52	55	I31	residue_name_number	Hydrophobic packing between the side chains of F20, I31, and E22 stabilizes these interfaces (Figure 5D and E).	RESULTS
61	64	E22	residue_name_number	Hydrophobic packing between the side chains of F20, I31, and E22 stabilizes these interfaces (Figure 5D and E).	RESULTS
82	92	interfaces	site	Hydrophobic packing between the side chains of F20, I31, and E22 stabilizes these interfaces (Figure 5D and E).	RESULTS
4	16	annular pore	site	The annular pore contains three eclipsed interfaces and two staggered interfaces.	RESULTS
32	40	eclipsed	protein_state	The annular pore contains three eclipsed interfaces and two staggered interfaces.	RESULTS
41	51	interfaces	site	The annular pore contains three eclipsed interfaces and two staggered interfaces.	RESULTS
60	69	staggered	protein_state	The annular pore contains three eclipsed interfaces and two staggered interfaces.	RESULTS
70	80	interfaces	site	The annular pore contains three eclipsed interfaces and two staggered interfaces.	RESULTS
4	12	eclipsed	protein_state	The eclipsed interfaces occur between dodecamers 1 and 2, 1 and 5, and 3 and 4, as shown in Figure 5A.	RESULTS
13	23	interfaces	site	The eclipsed interfaces occur between dodecamers 1 and 2, 1 and 5, and 3 and 4, as shown in Figure 5A.	RESULTS
38	56	dodecamers 1 and 2	structure_element	The eclipsed interfaces occur between dodecamers 1 and 2, 1 and 5, and 3 and 4, as shown in Figure 5A.	RESULTS
58	65	1 and 5	structure_element	The eclipsed interfaces occur between dodecamers 1 and 2, 1 and 5, and 3 and 4, as shown in Figure 5A.	RESULTS
71	78	3 and 4	structure_element	The eclipsed interfaces occur between dodecamers 1 and 2, 1 and 5, and 3 and 4, as shown in Figure 5A.	RESULTS
4	13	staggered	protein_state	The staggered interfaces occur between dodecamers 2 and 3 and 4 and 5.	RESULTS
14	24	interfaces	site	The staggered interfaces occur between dodecamers 2 and 3 and 4 and 5.	RESULTS
39	57	dodecamers 2 and 3	structure_element	The staggered interfaces occur between dodecamers 2 and 3 and 4 and 5.	RESULTS
62	69	4 and 5	structure_element	The staggered interfaces occur between dodecamers 2 and 3 and 4 and 5.	RESULTS
4	16	annular pore	site	The annular pore is not completely flat, instead, adopting a slightly puckered shape, which accommodates the eclipsed and staggered interfaces.	RESULTS
109	117	eclipsed	protein_state	The annular pore is not completely flat, instead, adopting a slightly puckered shape, which accommodates the eclipsed and staggered interfaces.	RESULTS
122	131	staggered	protein_state	The annular pore is not completely flat, instead, adopting a slightly puckered shape, which accommodates the eclipsed and staggered interfaces.	RESULTS
132	142	interfaces	site	The annular pore is not completely flat, instead, adopting a slightly puckered shape, which accommodates the eclipsed and staggered interfaces.	RESULTS
4	6	Aβ	protein	Ten Aβ25–28 loops from the vertices of the five dodecamers line the hole in the center of the pore.	RESULTS
6	11	25–28	residue_range	Ten Aβ25–28 loops from the vertices of the five dodecamers line the hole in the center of the pore.	RESULTS
12	17	loops	structure_element	Ten Aβ25–28 loops from the vertices of the five dodecamers line the hole in the center of the pore.	RESULTS
48	58	dodecamers	oligomeric_state	Ten Aβ25–28 loops from the vertices of the five dodecamers line the hole in the center of the pore.	RESULTS
94	98	pore	site	Ten Aβ25–28 loops from the vertices of the five dodecamers line the hole in the center of the pore.	RESULTS
31	34	S26	residue_name_number	The hydrophilic side chains of S26, N27, and K28 decorate the hole.	RESULTS
36	39	N27	residue_name_number	The hydrophilic side chains of S26, N27, and K28 decorate the hole.	RESULTS
45	48	K28	residue_name_number	The hydrophilic side chains of S26, N27, and K28 decorate the hole.	RESULTS
0	32	X-ray crystallographic structure	evidence	X-ray crystallographic structure of the annular pore formed by peptide 2. (A) Annular porelike structure illustrating the relationship of the five dodecamers that form the pore (top view).	FIG
40	52	annular pore	site	X-ray crystallographic structure of the annular pore formed by peptide 2. (A) Annular porelike structure illustrating the relationship of the five dodecamers that form the pore (top view).	FIG
63	72	peptide 2	mutant	X-ray crystallographic structure of the annular pore formed by peptide 2. (A) Annular porelike structure illustrating the relationship of the five dodecamers that form the pore (top view).	FIG
78	94	Annular porelike	structure_element	X-ray crystallographic structure of the annular pore formed by peptide 2. (A) Annular porelike structure illustrating the relationship of the five dodecamers that form the pore (top view).	FIG
95	104	structure	evidence	X-ray crystallographic structure of the annular pore formed by peptide 2. (A) Annular porelike structure illustrating the relationship of the five dodecamers that form the pore (top view).	FIG
147	157	dodecamers	oligomeric_state	X-ray crystallographic structure of the annular pore formed by peptide 2. (A) Annular porelike structure illustrating the relationship of the five dodecamers that form the pore (top view).	FIG
172	176	pore	site	X-ray crystallographic structure of the annular pore formed by peptide 2. (A) Annular porelike structure illustrating the relationship of the five dodecamers that form the pore (top view).	FIG
5	23	Eclipsed interface	site	 (B) Eclipsed interface between dodecamers 1 and 2 (side view).	FIG
32	50	dodecamers 1 and 2	structure_element	 (B) Eclipsed interface between dodecamers 1 and 2 (side view).	FIG
9	27	eclipsed interface	site	The same eclipsed interface also occurs between dodecamers 1 and 5 and 3 and 4. (C) Staggered interface between dodecamers 2 and 3 (side view).	FIG
48	66	dodecamers 1 and 5	structure_element	The same eclipsed interface also occurs between dodecamers 1 and 5 and 3 and 4. (C) Staggered interface between dodecamers 2 and 3 (side view).	FIG
71	78	3 and 4	structure_element	The same eclipsed interface also occurs between dodecamers 1 and 5 and 3 and 4. (C) Staggered interface between dodecamers 2 and 3 (side view).	FIG
84	103	Staggered interface	site	The same eclipsed interface also occurs between dodecamers 1 and 5 and 3 and 4. (C) Staggered interface between dodecamers 2 and 3 (side view).	FIG
112	130	dodecamers 2 and 3	structure_element	The same eclipsed interface also occurs between dodecamers 1 and 5 and 3 and 4. (C) Staggered interface between dodecamers 2 and 3 (side view).	FIG
9	28	staggered interface	site	The same staggered interface also occurs between dodecamers 4 and 5. (D) Eclipsed interface between dodecamers 1 and 5 (top view).	FIG
73	91	Eclipsed interface	site	The same staggered interface also occurs between dodecamers 4 and 5. (D) Eclipsed interface between dodecamers 1 and 5 (top view).	FIG
100	118	dodecamers 1 and 5	structure_element	The same staggered interface also occurs between dodecamers 4 and 5. (D) Eclipsed interface between dodecamers 1 and 5 (top view).	FIG
4	16	annular pore	site	The annular pore is comparable in size to other large protein assemblies.	RESULTS
46	50	pore	site	The diameter of the hole in the center of the pore is ∼2 nm.	RESULTS
21	25	pore	site	The thickness of the pore is ∼5 nm, which is comparable to that of a lipid bilayer membrane.	RESULTS
33	45	annular pore	site	It is important to note that the annular pore formed by peptide 2 is not a discrete unit in the crystal lattice.	RESULTS
56	65	peptide 2	mutant	It is important to note that the annular pore formed by peptide 2 is not a discrete unit in the crystal lattice.	RESULTS
96	111	crystal lattice	evidence	It is important to note that the annular pore formed by peptide 2 is not a discrete unit in the crystal lattice.	RESULTS
12	27	crystal lattice	evidence	Rather, the crystal lattice is composed of conjoined annular pores in which all four F20 faces on the surface of each dodecamer contact F20 faces on other dodecamers (Figure S4).	RESULTS
53	66	annular pores	site	Rather, the crystal lattice is composed of conjoined annular pores in which all four F20 faces on the surface of each dodecamer contact F20 faces on other dodecamers (Figure S4).	RESULTS
85	88	F20	residue_name_number	Rather, the crystal lattice is composed of conjoined annular pores in which all four F20 faces on the surface of each dodecamer contact F20 faces on other dodecamers (Figure S4).	RESULTS
118	127	dodecamer	oligomeric_state	Rather, the crystal lattice is composed of conjoined annular pores in which all four F20 faces on the surface of each dodecamer contact F20 faces on other dodecamers (Figure S4).	RESULTS
136	139	F20	residue_name_number	Rather, the crystal lattice is composed of conjoined annular pores in which all four F20 faces on the surface of each dodecamer contact F20 faces on other dodecamers (Figure S4).	RESULTS
155	165	dodecamers	oligomeric_state	Rather, the crystal lattice is composed of conjoined annular pores in which all four F20 faces on the surface of each dodecamer contact F20 faces on other dodecamers (Figure S4).	RESULTS
4	19	crystal lattice	evidence	The crystal lattice shows how the dodecamers can further assemble to form larger structures.	RESULTS
34	44	dodecamers	oligomeric_state	The crystal lattice shows how the dodecamers can further assemble to form larger structures.	RESULTS
5	14	dodecamer	oligomeric_state	Each dodecamer may be thought of as a tetravalent building block with the potential to assemble on all four faces to form higher-order supramolecular assemblies.	RESULTS
4	32	X-ray crystallographic study	experimental_method	The X-ray crystallographic study of peptide 2 described here provides high-resolution structures of oligomers formed by an Aβ17–36 β-hairpin.	DISCUSS
36	45	peptide 2	mutant	The X-ray crystallographic study of peptide 2 described here provides high-resolution structures of oligomers formed by an Aβ17–36 β-hairpin.	DISCUSS
86	96	structures	evidence	The X-ray crystallographic study of peptide 2 described here provides high-resolution structures of oligomers formed by an Aβ17–36 β-hairpin.	DISCUSS
100	109	oligomers	oligomeric_state	The X-ray crystallographic study of peptide 2 described here provides high-resolution structures of oligomers formed by an Aβ17–36 β-hairpin.	DISCUSS
123	125	Aβ	protein	The X-ray crystallographic study of peptide 2 described here provides high-resolution structures of oligomers formed by an Aβ17–36 β-hairpin.	DISCUSS
125	130	17–36	residue_range	The X-ray crystallographic study of peptide 2 described here provides high-resolution structures of oligomers formed by an Aβ17–36 β-hairpin.	DISCUSS
131	140	β-hairpin	structure_element	The X-ray crystallographic study of peptide 2 described here provides high-resolution structures of oligomers formed by an Aβ17–36 β-hairpin.	DISCUSS
4	29	crystallographic assembly	evidence	The crystallographic assembly of peptide 2 into a trimer, dodecamer, and annular pore provides a model for the assembly of the full-length Aβ peptide to form oligomers.	DISCUSS
33	42	peptide 2	mutant	The crystallographic assembly of peptide 2 into a trimer, dodecamer, and annular pore provides a model for the assembly of the full-length Aβ peptide to form oligomers.	DISCUSS
50	56	trimer	oligomeric_state	The crystallographic assembly of peptide 2 into a trimer, dodecamer, and annular pore provides a model for the assembly of the full-length Aβ peptide to form oligomers.	DISCUSS
58	67	dodecamer	oligomeric_state	The crystallographic assembly of peptide 2 into a trimer, dodecamer, and annular pore provides a model for the assembly of the full-length Aβ peptide to form oligomers.	DISCUSS
73	85	annular pore	site	The crystallographic assembly of peptide 2 into a trimer, dodecamer, and annular pore provides a model for the assembly of the full-length Aβ peptide to form oligomers.	DISCUSS
127	138	full-length	protein_state	The crystallographic assembly of peptide 2 into a trimer, dodecamer, and annular pore provides a model for the assembly of the full-length Aβ peptide to form oligomers.	DISCUSS
139	141	Aβ	protein	The crystallographic assembly of peptide 2 into a trimer, dodecamer, and annular pore provides a model for the assembly of the full-length Aβ peptide to form oligomers.	DISCUSS
158	167	oligomers	oligomeric_state	The crystallographic assembly of peptide 2 into a trimer, dodecamer, and annular pore provides a model for the assembly of the full-length Aβ peptide to form oligomers.	DISCUSS
14	16	Aβ	protein	In this model Aβ folds to form a β-hairpin comprising the hydrophobic central and C-terminal regions.	DISCUSS
33	42	β-hairpin	structure_element	In this model Aβ folds to form a β-hairpin comprising the hydrophobic central and C-terminal regions.	DISCUSS
70	100	central and C-terminal regions	structure_element	In this model Aβ folds to form a β-hairpin comprising the hydrophobic central and C-terminal regions.	DISCUSS
6	16	β-hairpins	structure_element	Three β-hairpins assemble to form a trimer, and four trimers assemble to form a dodecamer.	DISCUSS
36	42	trimer	oligomeric_state	Three β-hairpins assemble to form a trimer, and four trimers assemble to form a dodecamer.	DISCUSS
53	60	trimers	oligomeric_state	Three β-hairpins assemble to form a trimer, and four trimers assemble to form a dodecamer.	DISCUSS
80	89	dodecamer	oligomeric_state	Three β-hairpins assemble to form a trimer, and four trimers assemble to form a dodecamer.	DISCUSS
4	14	dodecamers	oligomeric_state	The dodecamers further assemble to form an annular pore (Figure 6).	DISCUSS
43	55	annular pore	site	The dodecamers further assemble to form an annular pore (Figure 6).	DISCUSS
42	44	Aβ	protein	Model for the hierarchical assembly of an Aβ β-hairpin into a trimer, dodecamer, and annular pore based on the crystallographic assembly of peptide 2.	FIG
45	54	β-hairpin	structure_element	Model for the hierarchical assembly of an Aβ β-hairpin into a trimer, dodecamer, and annular pore based on the crystallographic assembly of peptide 2.	FIG
62	68	trimer	oligomeric_state	Model for the hierarchical assembly of an Aβ β-hairpin into a trimer, dodecamer, and annular pore based on the crystallographic assembly of peptide 2.	FIG
70	79	dodecamer	oligomeric_state	Model for the hierarchical assembly of an Aβ β-hairpin into a trimer, dodecamer, and annular pore based on the crystallographic assembly of peptide 2.	FIG
85	97	annular pore	site	Model for the hierarchical assembly of an Aβ β-hairpin into a trimer, dodecamer, and annular pore based on the crystallographic assembly of peptide 2.	FIG
140	149	peptide 2	mutant	Model for the hierarchical assembly of an Aβ β-hairpin into a trimer, dodecamer, and annular pore based on the crystallographic assembly of peptide 2.	FIG
0	9	Monomeric	oligomeric_state	Monomeric Aβ folds to form a β-hairpin in which the hydrophobic central and C-terminal regions form an antiparallel β-sheet.	FIG
10	12	Aβ	protein	Monomeric Aβ folds to form a β-hairpin in which the hydrophobic central and C-terminal regions form an antiparallel β-sheet.	FIG
29	38	β-hairpin	structure_element	Monomeric Aβ folds to form a β-hairpin in which the hydrophobic central and C-terminal regions form an antiparallel β-sheet.	FIG
64	71	central	structure_element	Monomeric Aβ folds to form a β-hairpin in which the hydrophobic central and C-terminal regions form an antiparallel β-sheet.	FIG
76	94	C-terminal regions	structure_element	Monomeric Aβ folds to form a β-hairpin in which the hydrophobic central and C-terminal regions form an antiparallel β-sheet.	FIG
103	123	antiparallel β-sheet	structure_element	Monomeric Aβ folds to form a β-hairpin in which the hydrophobic central and C-terminal regions form an antiparallel β-sheet.	FIG
6	15	β-hairpin	structure_element	Three β-hairpin monomers assemble to form a triangular trimer.	FIG
16	24	monomers	oligomeric_state	Three β-hairpin monomers assemble to form a triangular trimer.	FIG
44	54	triangular	protein_state	Three β-hairpin monomers assemble to form a triangular trimer.	FIG
55	61	trimer	oligomeric_state	Three β-hairpin monomers assemble to form a triangular trimer.	FIG
5	15	triangular	protein_state	Four triangular trimers assemble to form a dodecamer.	FIG
16	23	trimers	oligomeric_state	Four triangular trimers assemble to form a dodecamer.	FIG
43	52	dodecamer	oligomeric_state	Four triangular trimers assemble to form a dodecamer.	FIG
5	15	dodecamers	oligomeric_state	Five dodecamers assemble to form an annular pore.	FIG
36	48	annular pore	site	Five dodecamers assemble to form an annular pore.	FIG
45	49	Aβ42	protein	The molecular weights shown correspond to an Aβ42 monomer (∼4.5 kDa), an Aβ42 trimer (∼13.5 kDa), an Aβ42 dodecamer (∼54 kDa), and an Aβ42 annular pore composed of five dodecamers (∼270 kDa).	FIG
50	57	monomer	oligomeric_state	The molecular weights shown correspond to an Aβ42 monomer (∼4.5 kDa), an Aβ42 trimer (∼13.5 kDa), an Aβ42 dodecamer (∼54 kDa), and an Aβ42 annular pore composed of five dodecamers (∼270 kDa).	FIG
73	77	Aβ42	protein	The molecular weights shown correspond to an Aβ42 monomer (∼4.5 kDa), an Aβ42 trimer (∼13.5 kDa), an Aβ42 dodecamer (∼54 kDa), and an Aβ42 annular pore composed of five dodecamers (∼270 kDa).	FIG
78	84	trimer	oligomeric_state	The molecular weights shown correspond to an Aβ42 monomer (∼4.5 kDa), an Aβ42 trimer (∼13.5 kDa), an Aβ42 dodecamer (∼54 kDa), and an Aβ42 annular pore composed of five dodecamers (∼270 kDa).	FIG
101	105	Aβ42	protein	The molecular weights shown correspond to an Aβ42 monomer (∼4.5 kDa), an Aβ42 trimer (∼13.5 kDa), an Aβ42 dodecamer (∼54 kDa), and an Aβ42 annular pore composed of five dodecamers (∼270 kDa).	FIG
106	115	dodecamer	oligomeric_state	The molecular weights shown correspond to an Aβ42 monomer (∼4.5 kDa), an Aβ42 trimer (∼13.5 kDa), an Aβ42 dodecamer (∼54 kDa), and an Aβ42 annular pore composed of five dodecamers (∼270 kDa).	FIG
134	138	Aβ42	protein	The molecular weights shown correspond to an Aβ42 monomer (∼4.5 kDa), an Aβ42 trimer (∼13.5 kDa), an Aβ42 dodecamer (∼54 kDa), and an Aβ42 annular pore composed of five dodecamers (∼270 kDa).	FIG
139	151	annular pore	site	The molecular weights shown correspond to an Aβ42 monomer (∼4.5 kDa), an Aβ42 trimer (∼13.5 kDa), an Aβ42 dodecamer (∼54 kDa), and an Aβ42 annular pore composed of five dodecamers (∼270 kDa).	FIG
169	179	dodecamers	oligomeric_state	The molecular weights shown correspond to an Aβ42 monomer (∼4.5 kDa), an Aβ42 trimer (∼13.5 kDa), an Aβ42 dodecamer (∼54 kDa), and an Aβ42 annular pore composed of five dodecamers (∼270 kDa).	FIG
91	93	Aβ	protein	The model put forth in Figure 6 is consistent with the current understanding of endogenous Aβ oligomerization and explains at atomic resolution many key observations about Aβ oligomers.	DISCUSS
172	174	Aβ	protein	The model put forth in Figure 6 is consistent with the current understanding of endogenous Aβ oligomerization and explains at atomic resolution many key observations about Aβ oligomers.	DISCUSS
175	184	oligomers	oligomeric_state	The model put forth in Figure 6 is consistent with the current understanding of endogenous Aβ oligomerization and explains at atomic resolution many key observations about Aβ oligomers.	DISCUSS
32	34	Aβ	protein	Two general types of endogenous Aβ oligomers have been observed: Aβ oligomers that occur on a pathway to fibrils, or “fibrillar oligomers”, and Aβ oligomers that evade a fibrillar fate, or “nonfibrillar oligomers”.− Fibrillar oligomers accumulate in Alzheimer’s disease later than nonfibrillar oligomers and coincide with the deposition of plaques.	DISCUSS
35	44	oligomers	oligomeric_state	Two general types of endogenous Aβ oligomers have been observed: Aβ oligomers that occur on a pathway to fibrils, or “fibrillar oligomers”, and Aβ oligomers that evade a fibrillar fate, or “nonfibrillar oligomers”.− Fibrillar oligomers accumulate in Alzheimer’s disease later than nonfibrillar oligomers and coincide with the deposition of plaques.	DISCUSS
65	67	Aβ	protein	Two general types of endogenous Aβ oligomers have been observed: Aβ oligomers that occur on a pathway to fibrils, or “fibrillar oligomers”, and Aβ oligomers that evade a fibrillar fate, or “nonfibrillar oligomers”.− Fibrillar oligomers accumulate in Alzheimer’s disease later than nonfibrillar oligomers and coincide with the deposition of plaques.	DISCUSS
68	77	oligomers	oligomeric_state	Two general types of endogenous Aβ oligomers have been observed: Aβ oligomers that occur on a pathway to fibrils, or “fibrillar oligomers”, and Aβ oligomers that evade a fibrillar fate, or “nonfibrillar oligomers”.− Fibrillar oligomers accumulate in Alzheimer’s disease later than nonfibrillar oligomers and coincide with the deposition of plaques.	DISCUSS
105	112	fibrils	oligomeric_state	Two general types of endogenous Aβ oligomers have been observed: Aβ oligomers that occur on a pathway to fibrils, or “fibrillar oligomers”, and Aβ oligomers that evade a fibrillar fate, or “nonfibrillar oligomers”.− Fibrillar oligomers accumulate in Alzheimer’s disease later than nonfibrillar oligomers and coincide with the deposition of plaques.	DISCUSS
118	127	fibrillar	protein_state	Two general types of endogenous Aβ oligomers have been observed: Aβ oligomers that occur on a pathway to fibrils, or “fibrillar oligomers”, and Aβ oligomers that evade a fibrillar fate, or “nonfibrillar oligomers”.− Fibrillar oligomers accumulate in Alzheimer’s disease later than nonfibrillar oligomers and coincide with the deposition of plaques.	DISCUSS
128	137	oligomers	oligomeric_state	Two general types of endogenous Aβ oligomers have been observed: Aβ oligomers that occur on a pathway to fibrils, or “fibrillar oligomers”, and Aβ oligomers that evade a fibrillar fate, or “nonfibrillar oligomers”.− Fibrillar oligomers accumulate in Alzheimer’s disease later than nonfibrillar oligomers and coincide with the deposition of plaques.	DISCUSS
144	146	Aβ	protein	Two general types of endogenous Aβ oligomers have been observed: Aβ oligomers that occur on a pathway to fibrils, or “fibrillar oligomers”, and Aβ oligomers that evade a fibrillar fate, or “nonfibrillar oligomers”.− Fibrillar oligomers accumulate in Alzheimer’s disease later than nonfibrillar oligomers and coincide with the deposition of plaques.	DISCUSS
147	156	oligomers	oligomeric_state	Two general types of endogenous Aβ oligomers have been observed: Aβ oligomers that occur on a pathway to fibrils, or “fibrillar oligomers”, and Aβ oligomers that evade a fibrillar fate, or “nonfibrillar oligomers”.− Fibrillar oligomers accumulate in Alzheimer’s disease later than nonfibrillar oligomers and coincide with the deposition of plaques.	DISCUSS
170	179	fibrillar	protein_state	Two general types of endogenous Aβ oligomers have been observed: Aβ oligomers that occur on a pathway to fibrils, or “fibrillar oligomers”, and Aβ oligomers that evade a fibrillar fate, or “nonfibrillar oligomers”.− Fibrillar oligomers accumulate in Alzheimer’s disease later than nonfibrillar oligomers and coincide with the deposition of plaques.	DISCUSS
190	202	nonfibrillar	protein_state	Two general types of endogenous Aβ oligomers have been observed: Aβ oligomers that occur on a pathway to fibrils, or “fibrillar oligomers”, and Aβ oligomers that evade a fibrillar fate, or “nonfibrillar oligomers”.− Fibrillar oligomers accumulate in Alzheimer’s disease later than nonfibrillar oligomers and coincide with the deposition of plaques.	DISCUSS
203	212	oligomers	oligomeric_state	Two general types of endogenous Aβ oligomers have been observed: Aβ oligomers that occur on a pathway to fibrils, or “fibrillar oligomers”, and Aβ oligomers that evade a fibrillar fate, or “nonfibrillar oligomers”.− Fibrillar oligomers accumulate in Alzheimer’s disease later than nonfibrillar oligomers and coincide with the deposition of plaques.	DISCUSS
216	225	Fibrillar	protein_state	Two general types of endogenous Aβ oligomers have been observed: Aβ oligomers that occur on a pathway to fibrils, or “fibrillar oligomers”, and Aβ oligomers that evade a fibrillar fate, or “nonfibrillar oligomers”.− Fibrillar oligomers accumulate in Alzheimer’s disease later than nonfibrillar oligomers and coincide with the deposition of plaques.	DISCUSS
226	235	oligomers	oligomeric_state	Two general types of endogenous Aβ oligomers have been observed: Aβ oligomers that occur on a pathway to fibrils, or “fibrillar oligomers”, and Aβ oligomers that evade a fibrillar fate, or “nonfibrillar oligomers”.− Fibrillar oligomers accumulate in Alzheimer’s disease later than nonfibrillar oligomers and coincide with the deposition of plaques.	DISCUSS
281	293	nonfibrillar	protein_state	Two general types of endogenous Aβ oligomers have been observed: Aβ oligomers that occur on a pathway to fibrils, or “fibrillar oligomers”, and Aβ oligomers that evade a fibrillar fate, or “nonfibrillar oligomers”.− Fibrillar oligomers accumulate in Alzheimer’s disease later than nonfibrillar oligomers and coincide with the deposition of plaques.	DISCUSS
294	303	oligomers	oligomeric_state	Two general types of endogenous Aβ oligomers have been observed: Aβ oligomers that occur on a pathway to fibrils, or “fibrillar oligomers”, and Aβ oligomers that evade a fibrillar fate, or “nonfibrillar oligomers”.− Fibrillar oligomers accumulate in Alzheimer’s disease later than nonfibrillar oligomers and coincide with the deposition of plaques.	DISCUSS
0	12	Nonfibrillar	protein_state	Nonfibrillar oligomers accumulate early in Alzheimer’s disease before plaque deposition.	DISCUSS
13	22	oligomers	oligomeric_state	Nonfibrillar oligomers accumulate early in Alzheimer’s disease before plaque deposition.	DISCUSS
0	9	Fibrillar	protein_state	Fibrillar and nonfibrillar oligomers have structurally distinct characteristics, which are reflected in their reactivity with the fibril-specific OC antibody and the oligomer-specific A11 antibody.	DISCUSS
14	26	nonfibrillar	protein_state	Fibrillar and nonfibrillar oligomers have structurally distinct characteristics, which are reflected in their reactivity with the fibril-specific OC antibody and the oligomer-specific A11 antibody.	DISCUSS
27	36	oligomers	oligomeric_state	Fibrillar and nonfibrillar oligomers have structurally distinct characteristics, which are reflected in their reactivity with the fibril-specific OC antibody and the oligomer-specific A11 antibody.	DISCUSS
166	174	oligomer	oligomeric_state	Fibrillar and nonfibrillar oligomers have structurally distinct characteristics, which are reflected in their reactivity with the fibril-specific OC antibody and the oligomer-specific A11 antibody.	DISCUSS
0	9	Fibrillar	protein_state	Fibrillar oligomers are recognized by the OC antibody but not the A11 antibody, whereas nonfibrillar oligomers are recognized by the A11 antibody but not the OC antibody.	DISCUSS
10	19	oligomers	oligomeric_state	Fibrillar oligomers are recognized by the OC antibody but not the A11 antibody, whereas nonfibrillar oligomers are recognized by the A11 antibody but not the OC antibody.	DISCUSS
88	100	nonfibrillar	protein_state	Fibrillar oligomers are recognized by the OC antibody but not the A11 antibody, whereas nonfibrillar oligomers are recognized by the A11 antibody but not the OC antibody.	DISCUSS
101	110	oligomers	oligomeric_state	Fibrillar oligomers are recognized by the OC antibody but not the A11 antibody, whereas nonfibrillar oligomers are recognized by the A11 antibody but not the OC antibody.	DISCUSS
46	48	Aβ	protein	These criteria have been used to classify the Aβ oligomers that accumulate in vivo.	DISCUSS
49	58	oligomers	oligomeric_state	These criteria have been used to classify the Aβ oligomers that accumulate in vivo.	DISCUSS
0	2	Aβ	protein	Aβ dimers have been classified as fibrillar oligomers, whereas Aβ trimers, Aβ*56, and APFs have been classified as nonfibrillar oligomers.	DISCUSS
3	9	dimers	oligomeric_state	Aβ dimers have been classified as fibrillar oligomers, whereas Aβ trimers, Aβ*56, and APFs have been classified as nonfibrillar oligomers.	DISCUSS
34	43	fibrillar	protein_state	Aβ dimers have been classified as fibrillar oligomers, whereas Aβ trimers, Aβ*56, and APFs have been classified as nonfibrillar oligomers.	DISCUSS
44	53	oligomers	oligomeric_state	Aβ dimers have been classified as fibrillar oligomers, whereas Aβ trimers, Aβ*56, and APFs have been classified as nonfibrillar oligomers.	DISCUSS
63	65	Aβ	protein	Aβ dimers have been classified as fibrillar oligomers, whereas Aβ trimers, Aβ*56, and APFs have been classified as nonfibrillar oligomers.	DISCUSS
66	73	trimers	oligomeric_state	Aβ dimers have been classified as fibrillar oligomers, whereas Aβ trimers, Aβ*56, and APFs have been classified as nonfibrillar oligomers.	DISCUSS
75	80	Aβ*56	complex_assembly	Aβ dimers have been classified as fibrillar oligomers, whereas Aβ trimers, Aβ*56, and APFs have been classified as nonfibrillar oligomers.	DISCUSS
86	90	APFs	complex_assembly	Aβ dimers have been classified as fibrillar oligomers, whereas Aβ trimers, Aβ*56, and APFs have been classified as nonfibrillar oligomers.	DISCUSS
115	127	nonfibrillar	protein_state	Aβ dimers have been classified as fibrillar oligomers, whereas Aβ trimers, Aβ*56, and APFs have been classified as nonfibrillar oligomers.	DISCUSS
128	137	oligomers	oligomeric_state	Aβ dimers have been classified as fibrillar oligomers, whereas Aβ trimers, Aβ*56, and APFs have been classified as nonfibrillar oligomers.	DISCUSS
67	79	nonfibrillar	protein_state	Larson and Lesné proposed a model for the endogenous production of nonfibrillar oligomers that explains these observations.	DISCUSS
80	89	oligomers	oligomeric_state	Larson and Lesné proposed a model for the endogenous production of nonfibrillar oligomers that explains these observations.	DISCUSS
15	21	folded	protein_state	In this model, folded Aβ monomer assembles into a trimer, the trimer further assembles into hexamers and dodecamers, and the dodecamers further assemble to form annular protofibrils.	DISCUSS
22	24	Aβ	protein	In this model, folded Aβ monomer assembles into a trimer, the trimer further assembles into hexamers and dodecamers, and the dodecamers further assemble to form annular protofibrils.	DISCUSS
25	32	monomer	oligomeric_state	In this model, folded Aβ monomer assembles into a trimer, the trimer further assembles into hexamers and dodecamers, and the dodecamers further assemble to form annular protofibrils.	DISCUSS
50	56	trimer	oligomeric_state	In this model, folded Aβ monomer assembles into a trimer, the trimer further assembles into hexamers and dodecamers, and the dodecamers further assemble to form annular protofibrils.	DISCUSS
62	68	trimer	oligomeric_state	In this model, folded Aβ monomer assembles into a trimer, the trimer further assembles into hexamers and dodecamers, and the dodecamers further assemble to form annular protofibrils.	DISCUSS
92	100	hexamers	oligomeric_state	In this model, folded Aβ monomer assembles into a trimer, the trimer further assembles into hexamers and dodecamers, and the dodecamers further assemble to form annular protofibrils.	DISCUSS
105	115	dodecamers	oligomeric_state	In this model, folded Aβ monomer assembles into a trimer, the trimer further assembles into hexamers and dodecamers, and the dodecamers further assemble to form annular protofibrils.	DISCUSS
125	135	dodecamers	oligomeric_state	In this model, folded Aβ monomer assembles into a trimer, the trimer further assembles into hexamers and dodecamers, and the dodecamers further assemble to form annular protofibrils.	DISCUSS
161	181	annular protofibrils	complex_assembly	In this model, folded Aβ monomer assembles into a trimer, the trimer further assembles into hexamers and dodecamers, and the dodecamers further assemble to form annular protofibrils.	DISCUSS
29	38	peptide 2	mutant	The hierarchical assembly of peptide 2 is consistent with this model; and the trimer, dodecamer, and annular pore formed by peptide 2 may share similarities to the trimers, Aβ*56, and APFs observed in vivo.	DISCUSS
78	84	trimer	oligomeric_state	The hierarchical assembly of peptide 2 is consistent with this model; and the trimer, dodecamer, and annular pore formed by peptide 2 may share similarities to the trimers, Aβ*56, and APFs observed in vivo.	DISCUSS
86	95	dodecamer	oligomeric_state	The hierarchical assembly of peptide 2 is consistent with this model; and the trimer, dodecamer, and annular pore formed by peptide 2 may share similarities to the trimers, Aβ*56, and APFs observed in vivo.	DISCUSS
101	113	annular pore	site	The hierarchical assembly of peptide 2 is consistent with this model; and the trimer, dodecamer, and annular pore formed by peptide 2 may share similarities to the trimers, Aβ*56, and APFs observed in vivo.	DISCUSS
124	133	peptide 2	mutant	The hierarchical assembly of peptide 2 is consistent with this model; and the trimer, dodecamer, and annular pore formed by peptide 2 may share similarities to the trimers, Aβ*56, and APFs observed in vivo.	DISCUSS
164	171	trimers	oligomeric_state	The hierarchical assembly of peptide 2 is consistent with this model; and the trimer, dodecamer, and annular pore formed by peptide 2 may share similarities to the trimers, Aβ*56, and APFs observed in vivo.	DISCUSS
173	178	Aβ*56	complex_assembly	The hierarchical assembly of peptide 2 is consistent with this model; and the trimer, dodecamer, and annular pore formed by peptide 2 may share similarities to the trimers, Aβ*56, and APFs observed in vivo.	DISCUSS
184	188	APFs	complex_assembly	The hierarchical assembly of peptide 2 is consistent with this model; and the trimer, dodecamer, and annular pore formed by peptide 2 may share similarities to the trimers, Aβ*56, and APFs observed in vivo.	DISCUSS
49	55	trimer	oligomeric_state	At this point, we can only speculate whether the trimer and dodecamer formed by peptide 2 share structural similarities to Aβ trimers and Aβ*56, as little is known about the structure of Aβ trimers and Aβ*56.	DISCUSS
60	69	dodecamer	oligomeric_state	At this point, we can only speculate whether the trimer and dodecamer formed by peptide 2 share structural similarities to Aβ trimers and Aβ*56, as little is known about the structure of Aβ trimers and Aβ*56.	DISCUSS
80	89	peptide 2	mutant	At this point, we can only speculate whether the trimer and dodecamer formed by peptide 2 share structural similarities to Aβ trimers and Aβ*56, as little is known about the structure of Aβ trimers and Aβ*56.	DISCUSS
123	125	Aβ	protein	At this point, we can only speculate whether the trimer and dodecamer formed by peptide 2 share structural similarities to Aβ trimers and Aβ*56, as little is known about the structure of Aβ trimers and Aβ*56.	DISCUSS
126	133	trimers	oligomeric_state	At this point, we can only speculate whether the trimer and dodecamer formed by peptide 2 share structural similarities to Aβ trimers and Aβ*56, as little is known about the structure of Aβ trimers and Aβ*56.	DISCUSS
138	143	Aβ*56	complex_assembly	At this point, we can only speculate whether the trimer and dodecamer formed by peptide 2 share structural similarities to Aβ trimers and Aβ*56, as little is known about the structure of Aβ trimers and Aβ*56.	DISCUSS
174	183	structure	evidence	At this point, we can only speculate whether the trimer and dodecamer formed by peptide 2 share structural similarities to Aβ trimers and Aβ*56, as little is known about the structure of Aβ trimers and Aβ*56.	DISCUSS
187	189	Aβ	protein	At this point, we can only speculate whether the trimer and dodecamer formed by peptide 2 share structural similarities to Aβ trimers and Aβ*56, as little is known about the structure of Aβ trimers and Aβ*56.	DISCUSS
190	197	trimers	oligomeric_state	At this point, we can only speculate whether the trimer and dodecamer formed by peptide 2 share structural similarities to Aβ trimers and Aβ*56, as little is known about the structure of Aβ trimers and Aβ*56.	DISCUSS
202	207	Aβ*56	complex_assembly	At this point, we can only speculate whether the trimer and dodecamer formed by peptide 2 share structural similarities to Aβ trimers and Aβ*56, as little is known about the structure of Aβ trimers and Aβ*56.	DISCUSS
4	33	crystallographically observed	evidence	The crystallographically observed annular pore formed by peptide 2 is morphologically similar to the APFs formed by full-length Aβ.	DISCUSS
34	46	annular pore	site	The crystallographically observed annular pore formed by peptide 2 is morphologically similar to the APFs formed by full-length Aβ.	DISCUSS
57	66	peptide 2	mutant	The crystallographically observed annular pore formed by peptide 2 is morphologically similar to the APFs formed by full-length Aβ.	DISCUSS
101	105	APFs	complex_assembly	The crystallographically observed annular pore formed by peptide 2 is morphologically similar to the APFs formed by full-length Aβ.	DISCUSS
116	127	full-length	protein_state	The crystallographically observed annular pore formed by peptide 2 is morphologically similar to the APFs formed by full-length Aβ.	DISCUSS
128	130	Aβ	protein	The crystallographically observed annular pore formed by peptide 2 is morphologically similar to the APFs formed by full-length Aβ.	DISCUSS
4	16	annular pore	site	The annular pore formed by peptide 2 is comparable in size to the APFs prepared in vitro or isolated from Alzheimer’s brains (Figure 7 and Table 1).	DISCUSS
27	36	peptide 2	mutant	The annular pore formed by peptide 2 is comparable in size to the APFs prepared in vitro or isolated from Alzheimer’s brains (Figure 7 and Table 1).	DISCUSS
66	70	APFs	complex_assembly	The annular pore formed by peptide 2 is comparable in size to the APFs prepared in vitro or isolated from Alzheimer’s brains (Figure 7 and Table 1).	DISCUSS
21	25	APFs	complex_assembly	The varying sizes of APFs formed by full-length Aβ might result from differences in the number of oligomer subunits comprising each APF.	DISCUSS
36	47	full-length	protein_state	The varying sizes of APFs formed by full-length Aβ might result from differences in the number of oligomer subunits comprising each APF.	DISCUSS
48	50	Aβ	protein	The varying sizes of APFs formed by full-length Aβ might result from differences in the number of oligomer subunits comprising each APF.	DISCUSS
98	106	oligomer	oligomeric_state	The varying sizes of APFs formed by full-length Aβ might result from differences in the number of oligomer subunits comprising each APF.	DISCUSS
107	115	subunits	structure_element	The varying sizes of APFs formed by full-length Aβ might result from differences in the number of oligomer subunits comprising each APF.	DISCUSS
132	135	APF	complex_assembly	The varying sizes of APFs formed by full-length Aβ might result from differences in the number of oligomer subunits comprising each APF.	DISCUSS
13	25	annular pore	site	Although the annular pore formed by peptide 2 contains five dodecamer subunits, pores containing fewer or more subunits can easily be envisioned.	DISCUSS
36	45	peptide 2	mutant	Although the annular pore formed by peptide 2 contains five dodecamer subunits, pores containing fewer or more subunits can easily be envisioned.	DISCUSS
60	69	dodecamer	oligomeric_state	Although the annular pore formed by peptide 2 contains five dodecamer subunits, pores containing fewer or more subunits can easily be envisioned.	DISCUSS
70	78	subunits	structure_element	Although the annular pore formed by peptide 2 contains five dodecamer subunits, pores containing fewer or more subunits can easily be envisioned.	DISCUSS
80	85	pores	site	Although the annular pore formed by peptide 2 contains five dodecamer subunits, pores containing fewer or more subunits can easily be envisioned.	DISCUSS
111	119	subunits	structure_element	Although the annular pore formed by peptide 2 contains five dodecamer subunits, pores containing fewer or more subunits can easily be envisioned.	DISCUSS
4	14	dodecamers	oligomeric_state	The dodecamers that comprise the annular pore exhibit two modes of assembly—eclipsed interactions and staggered interactions between the F20 faces of trimers within dodecamers.	DISCUSS
33	45	annular pore	site	The dodecamers that comprise the annular pore exhibit two modes of assembly—eclipsed interactions and staggered interactions between the F20 faces of trimers within dodecamers.	DISCUSS
76	84	eclipsed	protein_state	The dodecamers that comprise the annular pore exhibit two modes of assembly—eclipsed interactions and staggered interactions between the F20 faces of trimers within dodecamers.	DISCUSS
102	111	staggered	protein_state	The dodecamers that comprise the annular pore exhibit two modes of assembly—eclipsed interactions and staggered interactions between the F20 faces of trimers within dodecamers.	DISCUSS
137	140	F20	residue_name_number	The dodecamers that comprise the annular pore exhibit two modes of assembly—eclipsed interactions and staggered interactions between the F20 faces of trimers within dodecamers.	DISCUSS
150	157	trimers	oligomeric_state	The dodecamers that comprise the annular pore exhibit two modes of assembly—eclipsed interactions and staggered interactions between the F20 faces of trimers within dodecamers.	DISCUSS
165	175	dodecamers	oligomeric_state	The dodecamers that comprise the annular pore exhibit two modes of assembly—eclipsed interactions and staggered interactions between the F20 faces of trimers within dodecamers.	DISCUSS
72	82	dodecamers	oligomeric_state	These two modes of assembly might reflect a dynamic interaction between dodecamers, which could permit assemblies of more dodecamers into larger annular pores.	DISCUSS
122	132	dodecamers	oligomeric_state	These two modes of assembly might reflect a dynamic interaction between dodecamers, which could permit assemblies of more dodecamers into larger annular pores.	DISCUSS
145	158	annular pores	site	These two modes of assembly might reflect a dynamic interaction between dodecamers, which could permit assemblies of more dodecamers into larger annular pores.	DISCUSS
21	33	annular pore	site	Surface views of the annular pore formed by peptide 2. (A) Top view.	FIG
44	53	peptide 2	mutant	Surface views of the annular pore formed by peptide 2. (A) Top view.	FIG
0	13	Annular Pores	site	Annular Pores Formed by Aβ and Peptide 2	TABLE
24	26	Aβ	protein	Annular Pores Formed by Aβ and Peptide 2	TABLE
31	40	Peptide 2	mutant	Annular Pores Formed by Aβ and Peptide 2	TABLE
0	12	annular pore	site	"annular pore	 	source	outer diameter	inner diameter	observation	 	method	 	peptide 2	 ∼11–12 nm	∼2 nm	X-ray crystallography	 	synthetic Aβ	7–10 nm	1.5–2 nm	TEM	 	synthetic Aβ	16 nm	not reported	AFM	 	synthetic Aβ	8–25 nm	not reported	TEM	 	Alzheimer’s brain	11–14 nm	2.5–4 nm	TEM	 	"	TABLE
75	82	peptide	chemical	"annular pore	 	source	outer diameter	inner diameter	observation	 	method	 	peptide 2	 ∼11–12 nm	∼2 nm	X-ray crystallography	 	synthetic Aβ	7–10 nm	1.5–2 nm	TEM	 	synthetic Aβ	16 nm	not reported	AFM	 	synthetic Aβ	8–25 nm	not reported	TEM	 	Alzheimer’s brain	11–14 nm	2.5–4 nm	TEM	 	"	TABLE
102	123	X-ray crystallography	experimental_method	"annular pore	 	source	outer diameter	inner diameter	observation	 	method	 	peptide 2	 ∼11–12 nm	∼2 nm	X-ray crystallography	 	synthetic Aβ	7–10 nm	1.5–2 nm	TEM	 	synthetic Aβ	16 nm	not reported	AFM	 	synthetic Aβ	8–25 nm	not reported	TEM	 	Alzheimer’s brain	11–14 nm	2.5–4 nm	TEM	 	"	TABLE
126	135	synthetic	protein_state	"annular pore	 	source	outer diameter	inner diameter	observation	 	method	 	peptide 2	 ∼11–12 nm	∼2 nm	X-ray crystallography	 	synthetic Aβ	7–10 nm	1.5–2 nm	TEM	 	synthetic Aβ	16 nm	not reported	AFM	 	synthetic Aβ	8–25 nm	not reported	TEM	 	Alzheimer’s brain	11–14 nm	2.5–4 nm	TEM	 	"	TABLE
136	138	Aβ	protein	"annular pore	 	source	outer diameter	inner diameter	observation	 	method	 	peptide 2	 ∼11–12 nm	∼2 nm	X-ray crystallography	 	synthetic Aβ	7–10 nm	1.5–2 nm	TEM	 	synthetic Aβ	16 nm	not reported	AFM	 	synthetic Aβ	8–25 nm	not reported	TEM	 	Alzheimer’s brain	11–14 nm	2.5–4 nm	TEM	 	"	TABLE
156	159	TEM	experimental_method	"annular pore	 	source	outer diameter	inner diameter	observation	 	method	 	peptide 2	 ∼11–12 nm	∼2 nm	X-ray crystallography	 	synthetic Aβ	7–10 nm	1.5–2 nm	TEM	 	synthetic Aβ	16 nm	not reported	AFM	 	synthetic Aβ	8–25 nm	not reported	TEM	 	Alzheimer’s brain	11–14 nm	2.5–4 nm	TEM	 	"	TABLE
172	174	Aβ	protein	"annular pore	 	source	outer diameter	inner diameter	observation	 	method	 	peptide 2	 ∼11–12 nm	∼2 nm	X-ray crystallography	 	synthetic Aβ	7–10 nm	1.5–2 nm	TEM	 	synthetic Aβ	16 nm	not reported	AFM	 	synthetic Aβ	8–25 nm	not reported	TEM	 	Alzheimer’s brain	11–14 nm	2.5–4 nm	TEM	 	"	TABLE
194	197	AFM	experimental_method	"annular pore	 	source	outer diameter	inner diameter	observation	 	method	 	peptide 2	 ∼11–12 nm	∼2 nm	X-ray crystallography	 	synthetic Aβ	7–10 nm	1.5–2 nm	TEM	 	synthetic Aβ	16 nm	not reported	AFM	 	synthetic Aβ	8–25 nm	not reported	TEM	 	Alzheimer’s brain	11–14 nm	2.5–4 nm	TEM	 	"	TABLE
210	212	Aβ	protein	"annular pore	 	source	outer diameter	inner diameter	observation	 	method	 	peptide 2	 ∼11–12 nm	∼2 nm	X-ray crystallography	 	synthetic Aβ	7–10 nm	1.5–2 nm	TEM	 	synthetic Aβ	16 nm	not reported	AFM	 	synthetic Aβ	8–25 nm	not reported	TEM	 	Alzheimer’s brain	11–14 nm	2.5–4 nm	TEM	 	"	TABLE
234	237	TEM	experimental_method	"annular pore	 	source	outer diameter	inner diameter	observation	 	method	 	peptide 2	 ∼11–12 nm	∼2 nm	X-ray crystallography	 	synthetic Aβ	7–10 nm	1.5–2 nm	TEM	 	synthetic Aβ	16 nm	not reported	AFM	 	synthetic Aβ	8–25 nm	not reported	TEM	 	Alzheimer’s brain	11–14 nm	2.5–4 nm	TEM	 	"	TABLE
276	279	TEM	experimental_method	"annular pore	 	source	outer diameter	inner diameter	observation	 	method	 	peptide 2	 ∼11–12 nm	∼2 nm	X-ray crystallography	 	synthetic Aβ	7–10 nm	1.5–2 nm	TEM	 	synthetic Aβ	16 nm	not reported	AFM	 	synthetic Aβ	8–25 nm	not reported	TEM	 	Alzheimer’s brain	11–14 nm	2.5–4 nm	TEM	 	"	TABLE
0	8	Dot blot	experimental_method	Dot blot analysis shows that peptide 2 is reactive toward the A11 antibody (Figure S5).	DISCUSS
29	38	peptide 2	mutant	Dot blot analysis shows that peptide 2 is reactive toward the A11 antibody (Figure S5).	DISCUSS
30	39	peptide 2	mutant	This reactivity suggests that peptide 2 forms oligomers in solution that share structural similarities to the nonfibrillar oligomers formed by full-length Aβ.	DISCUSS
46	55	oligomers	oligomeric_state	This reactivity suggests that peptide 2 forms oligomers in solution that share structural similarities to the nonfibrillar oligomers formed by full-length Aβ.	DISCUSS
110	122	nonfibrillar	protein_state	This reactivity suggests that peptide 2 forms oligomers in solution that share structural similarities to the nonfibrillar oligomers formed by full-length Aβ.	DISCUSS
123	132	oligomers	oligomeric_state	This reactivity suggests that peptide 2 forms oligomers in solution that share structural similarities to the nonfibrillar oligomers formed by full-length Aβ.	DISCUSS
143	154	full-length	protein_state	This reactivity suggests that peptide 2 forms oligomers in solution that share structural similarities to the nonfibrillar oligomers formed by full-length Aβ.	DISCUSS
155	157	Aβ	protein	This reactivity suggests that peptide 2 forms oligomers in solution that share structural similarities to the nonfibrillar oligomers formed by full-length Aβ.	DISCUSS
57	66	peptide 2	mutant	Further studies are needed to elucidate the species that peptide 2 forms in solution and to study their biological properties.	DISCUSS
47	50	SEC	experimental_method	Preliminary attempts to study these species by SEC and SDS-PAGE have not provided a clear measure of the structures formed in solution.	DISCUSS
55	63	SDS-PAGE	experimental_method	Preliminary attempts to study these species by SEC and SDS-PAGE have not provided a clear measure of the structures formed in solution.	DISCUSS
105	115	structures	evidence	Preliminary attempts to study these species by SEC and SDS-PAGE have not provided a clear measure of the structures formed in solution.	DISCUSS
31	40	oligomers	oligomeric_state	The difficulty in studying the oligomers formed in solution may reflect the propensity of the dodecamer to assemble on all four F20 faces.	DISCUSS
94	103	dodecamer	oligomeric_state	The difficulty in studying the oligomers formed in solution may reflect the propensity of the dodecamer to assemble on all four F20 faces.	DISCUSS
128	131	F20	residue_name_number	The difficulty in studying the oligomers formed in solution may reflect the propensity of the dodecamer to assemble on all four F20 faces.	DISCUSS
4	36	X-ray crystallographic structure	evidence	The X-ray crystallographic structure and A11 reactivity of peptide 2 support the model proposed by Larsen and Lesné and suggest that β-hairpins constitute a fundamental building block for nonfibrillar oligomers.	DISCUSS
59	68	peptide 2	mutant	The X-ray crystallographic structure and A11 reactivity of peptide 2 support the model proposed by Larsen and Lesné and suggest that β-hairpins constitute a fundamental building block for nonfibrillar oligomers.	DISCUSS
133	143	β-hairpins	structure_element	The X-ray crystallographic structure and A11 reactivity of peptide 2 support the model proposed by Larsen and Lesné and suggest that β-hairpins constitute a fundamental building block for nonfibrillar oligomers.	DISCUSS
188	200	nonfibrillar	protein_state	The X-ray crystallographic structure and A11 reactivity of peptide 2 support the model proposed by Larsen and Lesné and suggest that β-hairpins constitute a fundamental building block for nonfibrillar oligomers.	DISCUSS
201	210	oligomers	oligomeric_state	The X-ray crystallographic structure and A11 reactivity of peptide 2 support the model proposed by Larsen and Lesné and suggest that β-hairpins constitute a fundamental building block for nonfibrillar oligomers.	DISCUSS
11	21	β-hairpins	structure_element	What makes β-hairpins special is that three β-hairpins can nestle together to form trimers, stabilized by a network of hydrogen bonds and hydrophobic interactions.	DISCUSS
44	54	β-hairpins	structure_element	What makes β-hairpins special is that three β-hairpins can nestle together to form trimers, stabilized by a network of hydrogen bonds and hydrophobic interactions.	DISCUSS
83	90	trimers	oligomeric_state	What makes β-hairpins special is that three β-hairpins can nestle together to form trimers, stabilized by a network of hydrogen bonds and hydrophobic interactions.	DISCUSS
119	133	hydrogen bonds	bond_interaction	What makes β-hairpins special is that three β-hairpins can nestle together to form trimers, stabilized by a network of hydrogen bonds and hydrophobic interactions.	DISCUSS
138	162	hydrophobic interactions	bond_interaction	What makes β-hairpins special is that three β-hairpins can nestle together to form trimers, stabilized by a network of hydrogen bonds and hydrophobic interactions.	DISCUSS
39	41	Aβ	protein	This mode of assembly is not unique to Aβ.	DISCUSS
4	17	foldon domain	structure_element	The foldon domain of bacteriophage T4 fibritin is composed of three β-hairpins that assemble into a triangular trimer similar to the triangular trimer formed by peptide 2.	DISCUSS
21	37	bacteriophage T4	species	The foldon domain of bacteriophage T4 fibritin is composed of three β-hairpins that assemble into a triangular trimer similar to the triangular trimer formed by peptide 2.	DISCUSS
38	46	fibritin	protein	The foldon domain of bacteriophage T4 fibritin is composed of three β-hairpins that assemble into a triangular trimer similar to the triangular trimer formed by peptide 2.	DISCUSS
68	78	β-hairpins	structure_element	The foldon domain of bacteriophage T4 fibritin is composed of three β-hairpins that assemble into a triangular trimer similar to the triangular trimer formed by peptide 2.	DISCUSS
100	110	triangular	protein_state	The foldon domain of bacteriophage T4 fibritin is composed of three β-hairpins that assemble into a triangular trimer similar to the triangular trimer formed by peptide 2.	DISCUSS
111	117	trimer	oligomeric_state	The foldon domain of bacteriophage T4 fibritin is composed of three β-hairpins that assemble into a triangular trimer similar to the triangular trimer formed by peptide 2.	DISCUSS
133	143	triangular	protein_state	The foldon domain of bacteriophage T4 fibritin is composed of three β-hairpins that assemble into a triangular trimer similar to the triangular trimer formed by peptide 2.	DISCUSS
144	150	trimer	oligomeric_state	The foldon domain of bacteriophage T4 fibritin is composed of three β-hairpins that assemble into a triangular trimer similar to the triangular trimer formed by peptide 2.	DISCUSS
161	170	peptide 2	mutant	The foldon domain of bacteriophage T4 fibritin is composed of three β-hairpins that assemble into a triangular trimer similar to the triangular trimer formed by peptide 2.	DISCUSS
70	79	β-hairpin	structure_element	Additionally, our research group has observed a similar assembly of a β-hairpin peptide derived from β2-microglobulin.	DISCUSS
101	117	β2-microglobulin	protein	Additionally, our research group has observed a similar assembly of a β-hairpin peptide derived from β2-microglobulin.	DISCUSS
77	84	trimers	oligomeric_state	Although we began these studies with a relatively simple hypothesis—that the trimers and dodecamers formed by peptide 1 could accommodate the Aβ24–29 loop—an even more exciting finding has emerged—that the dodecamers can assemble to form annular pores.	CONCL
89	99	dodecamers	oligomeric_state	Although we began these studies with a relatively simple hypothesis—that the trimers and dodecamers formed by peptide 1 could accommodate the Aβ24–29 loop—an even more exciting finding has emerged—that the dodecamers can assemble to form annular pores.	CONCL
110	119	peptide 1	mutant	Although we began these studies with a relatively simple hypothesis—that the trimers and dodecamers formed by peptide 1 could accommodate the Aβ24–29 loop—an even more exciting finding has emerged—that the dodecamers can assemble to form annular pores.	CONCL
142	144	Aβ	protein	Although we began these studies with a relatively simple hypothesis—that the trimers and dodecamers formed by peptide 1 could accommodate the Aβ24–29 loop—an even more exciting finding has emerged—that the dodecamers can assemble to form annular pores.	CONCL
144	149	24–29	residue_range	Although we began these studies with a relatively simple hypothesis—that the trimers and dodecamers formed by peptide 1 could accommodate the Aβ24–29 loop—an even more exciting finding has emerged—that the dodecamers can assemble to form annular pores.	CONCL
150	154	loop	structure_element	Although we began these studies with a relatively simple hypothesis—that the trimers and dodecamers formed by peptide 1 could accommodate the Aβ24–29 loop—an even more exciting finding has emerged—that the dodecamers can assemble to form annular pores.	CONCL
206	216	dodecamers	oligomeric_state	Although we began these studies with a relatively simple hypothesis—that the trimers and dodecamers formed by peptide 1 could accommodate the Aβ24–29 loop—an even more exciting finding has emerged—that the dodecamers can assemble to form annular pores.	CONCL
238	251	annular pores	site	Although we began these studies with a relatively simple hypothesis—that the trimers and dodecamers formed by peptide 1 could accommodate the Aβ24–29 loop—an even more exciting finding has emerged—that the dodecamers can assemble to form annular pores.	CONCL
54	86	X-ray crystallographic structure	evidence	This finding could not have been anticipated from the X-ray crystallographic structure of peptide 1 and reveals a new level of hierarchical assembly that recapitulates micrographic observations of annular protofibrils.	CONCL
90	99	peptide 1	mutant	This finding could not have been anticipated from the X-ray crystallographic structure of peptide 1 and reveals a new level of hierarchical assembly that recapitulates micrographic observations of annular protofibrils.	CONCL
197	217	annular protofibrils	complex_assembly	This finding could not have been anticipated from the X-ray crystallographic structure of peptide 1 and reveals a new level of hierarchical assembly that recapitulates micrographic observations of annular protofibrils.	CONCL
4	33	crystallographically observed	evidence	The crystallographically observed dodecamer, in turn, recapitulates the observation of Aβ*56, which appears to be a dodecamer of Aβ.	CONCL
34	43	dodecamer	oligomeric_state	The crystallographically observed dodecamer, in turn, recapitulates the observation of Aβ*56, which appears to be a dodecamer of Aβ.	CONCL
87	92	Aβ*56	complex_assembly	The crystallographically observed dodecamer, in turn, recapitulates the observation of Aβ*56, which appears to be a dodecamer of Aβ.	CONCL
116	125	dodecamer	oligomeric_state	The crystallographically observed dodecamer, in turn, recapitulates the observation of Aβ*56, which appears to be a dodecamer of Aβ.	CONCL
129	131	Aβ	protein	The crystallographically observed dodecamer, in turn, recapitulates the observation of Aβ*56, which appears to be a dodecamer of Aβ.	CONCL
4	33	crystallographically observed	evidence	The crystallographically observed trimer recapitulates the Aβ trimers that are observed even before the onset of symptoms in Alzheimer’s disease.	CONCL
34	40	trimer	oligomeric_state	The crystallographically observed trimer recapitulates the Aβ trimers that are observed even before the onset of symptoms in Alzheimer’s disease.	CONCL
59	61	Aβ	protein	The crystallographically observed trimer recapitulates the Aβ trimers that are observed even before the onset of symptoms in Alzheimer’s disease.	CONCL
62	69	trimers	oligomeric_state	The crystallographically observed trimer recapitulates the Aβ trimers that are observed even before the onset of symptoms in Alzheimer’s disease.	CONCL
29	31	Aβ	protein	Our approach of constraining Aβ17–36 into a β-hairpin conformation and blocking aggregation with an N-methyl group has allowed us to crystallize a large fragment of what is generally considered to be an uncrystallizable peptide.	CONCL
31	36	17–36	residue_range	Our approach of constraining Aβ17–36 into a β-hairpin conformation and blocking aggregation with an N-methyl group has allowed us to crystallize a large fragment of what is generally considered to be an uncrystallizable peptide.	CONCL
44	53	β-hairpin	structure_element	Our approach of constraining Aβ17–36 into a β-hairpin conformation and blocking aggregation with an N-methyl group has allowed us to crystallize a large fragment of what is generally considered to be an uncrystallizable peptide.	CONCL
133	144	crystallize	experimental_method	Our approach of constraining Aβ17–36 into a β-hairpin conformation and blocking aggregation with an N-methyl group has allowed us to crystallize a large fragment of what is generally considered to be an uncrystallizable peptide.	CONCL
100	111	crystallize	experimental_method	We believe this iterative, “bottom up” approach of identifying the minimal modification required to crystallize Aβ peptides will ultimately allow larger fragments of Aβ to be crystallized, thus providing greater insights into the structures of Aβ oligomers.	CONCL
112	114	Aβ	protein	We believe this iterative, “bottom up” approach of identifying the minimal modification required to crystallize Aβ peptides will ultimately allow larger fragments of Aβ to be crystallized, thus providing greater insights into the structures of Aβ oligomers.	CONCL
166	168	Aβ	protein	We believe this iterative, “bottom up” approach of identifying the minimal modification required to crystallize Aβ peptides will ultimately allow larger fragments of Aβ to be crystallized, thus providing greater insights into the structures of Aβ oligomers.	CONCL
175	187	crystallized	experimental_method	We believe this iterative, “bottom up” approach of identifying the minimal modification required to crystallize Aβ peptides will ultimately allow larger fragments of Aβ to be crystallized, thus providing greater insights into the structures of Aβ oligomers.	CONCL
230	240	structures	evidence	We believe this iterative, “bottom up” approach of identifying the minimal modification required to crystallize Aβ peptides will ultimately allow larger fragments of Aβ to be crystallized, thus providing greater insights into the structures of Aβ oligomers.	CONCL
244	246	Aβ	protein	We believe this iterative, “bottom up” approach of identifying the minimal modification required to crystallize Aβ peptides will ultimately allow larger fragments of Aβ to be crystallized, thus providing greater insights into the structures of Aβ oligomers.	CONCL
247	256	oligomers	oligomeric_state	We believe this iterative, “bottom up” approach of identifying the minimal modification required to crystallize Aβ peptides will ultimately allow larger fragments of Aβ to be crystallized, thus providing greater insights into the structures of Aβ oligomers.	CONCL