anno_start	anno_end	anno_text	entity_type	sentence	section
19	25	IL-17A	protein	Inhibiting complex IL-17A and IL-17RA interactions with a linear peptide	TITLE
30	37	IL-17RA	protein	Inhibiting complex IL-17A and IL-17RA interactions with a linear peptide	TITLE
65	72	peptide	chemical	Inhibiting complex IL-17A and IL-17RA interactions with a linear peptide	TITLE
0	6	IL-17A	protein	IL-17A is a pro-inflammatory cytokine that has been implicated in autoimmune and inflammatory diseases.	ABSTRACT
29	37	cytokine	protein_type	IL-17A is a pro-inflammatory cytokine that has been implicated in autoimmune and inflammatory diseases.	ABSTRACT
11	21	antibodies	protein_type	Monoclonal antibodies inhibiting IL-17A signaling have demonstrated remarkable efficacy, but an oral therapy is still lacking.	ABSTRACT
33	39	IL-17A	protein	Monoclonal antibodies inhibiting IL-17A signaling have demonstrated remarkable efficacy, but an oral therapy is still lacking.	ABSTRACT
2	41	high affinity IL-17A peptide antagonist	chemical	A high affinity IL-17A peptide antagonist (HAP) of 15 residues was identified through phage-display screening followed by saturation mutagenesis optimization and amino acid substitutions.	ABSTRACT
43	46	HAP	chemical	A high affinity IL-17A peptide antagonist (HAP) of 15 residues was identified through phage-display screening followed by saturation mutagenesis optimization and amino acid substitutions.	ABSTRACT
51	62	15 residues	residue_range	A high affinity IL-17A peptide antagonist (HAP) of 15 residues was identified through phage-display screening followed by saturation mutagenesis optimization and amino acid substitutions.	ABSTRACT
86	109	phage-display screening	experimental_method	A high affinity IL-17A peptide antagonist (HAP) of 15 residues was identified through phage-display screening followed by saturation mutagenesis optimization and amino acid substitutions.	ABSTRACT
122	157	saturation mutagenesis optimization	experimental_method	A high affinity IL-17A peptide antagonist (HAP) of 15 residues was identified through phage-display screening followed by saturation mutagenesis optimization and amino acid substitutions.	ABSTRACT
162	186	amino acid substitutions	experimental_method	A high affinity IL-17A peptide antagonist (HAP) of 15 residues was identified through phage-display screening followed by saturation mutagenesis optimization and amino acid substitutions.	ABSTRACT
0	3	HAP	chemical	HAP binds specifically to IL-17A and inhibits the interaction of the cytokine with its receptor, IL-17RA.	ABSTRACT
26	32	IL-17A	protein	HAP binds specifically to IL-17A and inhibits the interaction of the cytokine with its receptor, IL-17RA.	ABSTRACT
69	77	cytokine	protein_type	HAP binds specifically to IL-17A and inhibits the interaction of the cytokine with its receptor, IL-17RA.	ABSTRACT
87	95	receptor	protein_type	HAP binds specifically to IL-17A and inhibits the interaction of the cytokine with its receptor, IL-17RA.	ABSTRACT
97	104	IL-17RA	protein	HAP binds specifically to IL-17A and inhibits the interaction of the cytokine with its receptor, IL-17RA.	ABSTRACT
18	23	human	species	Tested in primary human cells, HAP blocked the production of multiple inflammatory cytokines.	ABSTRACT
31	34	HAP	chemical	Tested in primary human cells, HAP blocked the production of multiple inflammatory cytokines.	ABSTRACT
83	92	cytokines	protein_type	Tested in primary human cells, HAP blocked the production of multiple inflammatory cytokines.	ABSTRACT
0	25	Crystal structure studies	experimental_method	Crystal structure studies revealed that two HAP molecules bind to one IL-17A dimer symmetrically.	ABSTRACT
44	47	HAP	chemical	Crystal structure studies revealed that two HAP molecules bind to one IL-17A dimer symmetrically.	ABSTRACT
70	76	IL-17A	protein	Crystal structure studies revealed that two HAP molecules bind to one IL-17A dimer symmetrically.	ABSTRACT
77	82	dimer	oligomeric_state	Crystal structure studies revealed that two HAP molecules bind to one IL-17A dimer symmetrically.	ABSTRACT
27	30	HAP	chemical	The N-terminal portions of HAP form a β-strand that inserts between two IL-17A monomers while the C-terminal section forms an α helix that directly blocks IL-17RA from binding to the same region of IL-17A.	ABSTRACT
38	46	β-strand	structure_element	The N-terminal portions of HAP form a β-strand that inserts between two IL-17A monomers while the C-terminal section forms an α helix that directly blocks IL-17RA from binding to the same region of IL-17A.	ABSTRACT
72	78	IL-17A	protein	The N-terminal portions of HAP form a β-strand that inserts between two IL-17A monomers while the C-terminal section forms an α helix that directly blocks IL-17RA from binding to the same region of IL-17A.	ABSTRACT
79	87	monomers	oligomeric_state	The N-terminal portions of HAP form a β-strand that inserts between two IL-17A monomers while the C-terminal section forms an α helix that directly blocks IL-17RA from binding to the same region of IL-17A.	ABSTRACT
126	133	α helix	structure_element	The N-terminal portions of HAP form a β-strand that inserts between two IL-17A monomers while the C-terminal section forms an α helix that directly blocks IL-17RA from binding to the same region of IL-17A.	ABSTRACT
155	162	IL-17RA	protein	The N-terminal portions of HAP form a β-strand that inserts between two IL-17A monomers while the C-terminal section forms an α helix that directly blocks IL-17RA from binding to the same region of IL-17A.	ABSTRACT
198	204	IL-17A	protein	The N-terminal portions of HAP form a β-strand that inserts between two IL-17A monomers while the C-terminal section forms an α helix that directly blocks IL-17RA from binding to the same region of IL-17A.	ABSTRACT
14	29	IL-17 cytokines	protein_type	The family of IL-17 cytokines and receptors consists of six polypeptides, IL-17A-F, and five receptors, IL-17RA-E. IL-17A is secreted from activated Th17 cells, and several innate immune T cell types including macrophages, neutrophils, natural killer cells, and dendritic cells.	INTRO
74	82	IL-17A-F	protein	The family of IL-17 cytokines and receptors consists of six polypeptides, IL-17A-F, and five receptors, IL-17RA-E. IL-17A is secreted from activated Th17 cells, and several innate immune T cell types including macrophages, neutrophils, natural killer cells, and dendritic cells.	INTRO
104	113	IL-17RA-E	protein	The family of IL-17 cytokines and receptors consists of six polypeptides, IL-17A-F, and five receptors, IL-17RA-E. IL-17A is secreted from activated Th17 cells, and several innate immune T cell types including macrophages, neutrophils, natural killer cells, and dendritic cells.	INTRO
115	121	IL-17A	protein	The family of IL-17 cytokines and receptors consists of six polypeptides, IL-17A-F, and five receptors, IL-17RA-E. IL-17A is secreted from activated Th17 cells, and several innate immune T cell types including macrophages, neutrophils, natural killer cells, and dendritic cells.	INTRO
0	6	IL-17A	protein	IL-17A signals through a specific cell surface receptor complex which consists of IL-17RA and IL-17RC.	INTRO
47	55	receptor	protein_type	IL-17A signals through a specific cell surface receptor complex which consists of IL-17RA and IL-17RC.	INTRO
82	89	IL-17RA	protein	IL-17A signals through a specific cell surface receptor complex which consists of IL-17RA and IL-17RC.	INTRO
94	101	IL-17RC	protein	IL-17A signals through a specific cell surface receptor complex which consists of IL-17RA and IL-17RC.	INTRO
0	6	IL-17A	protein	IL-17A’s downstream signaling leads to increased production of inflammatory cytokines such as IL-6, IL-8, CCL-20 and CXCL1 by various mechanisms including stimulation of transcription and stabilization of mRNA.	INTRO
76	85	cytokines	protein_type	IL-17A’s downstream signaling leads to increased production of inflammatory cytokines such as IL-6, IL-8, CCL-20 and CXCL1 by various mechanisms including stimulation of transcription and stabilization of mRNA.	INTRO
94	98	IL-6	protein_type	IL-17A’s downstream signaling leads to increased production of inflammatory cytokines such as IL-6, IL-8, CCL-20 and CXCL1 by various mechanisms including stimulation of transcription and stabilization of mRNA.	INTRO
100	104	IL-8	protein_type	IL-17A’s downstream signaling leads to increased production of inflammatory cytokines such as IL-6, IL-8, CCL-20 and CXCL1 by various mechanisms including stimulation of transcription and stabilization of mRNA.	INTRO
106	112	CCL-20	protein_type	IL-17A’s downstream signaling leads to increased production of inflammatory cytokines such as IL-6, IL-8, CCL-20 and CXCL1 by various mechanisms including stimulation of transcription and stabilization of mRNA.	INTRO
117	122	CXCL1	protein_type	IL-17A’s downstream signaling leads to increased production of inflammatory cytokines such as IL-6, IL-8, CCL-20 and CXCL1 by various mechanisms including stimulation of transcription and stabilization of mRNA.	INTRO
205	209	mRNA	chemical	IL-17A’s downstream signaling leads to increased production of inflammatory cytokines such as IL-6, IL-8, CCL-20 and CXCL1 by various mechanisms including stimulation of transcription and stabilization of mRNA.	INTRO
58	65	IL-17RA	protein	Although various cell types have been reported to express IL-17RA, the highest responses to IL-17A come from epithelial cells, endothelial cells, keratinocytes and fibroblasts.	INTRO
92	98	IL-17A	protein	Although various cell types have been reported to express IL-17RA, the highest responses to IL-17A come from epithelial cells, endothelial cells, keratinocytes and fibroblasts.	INTRO
0	6	IL-17A	protein	IL-17A and its signaling is important in host defense against certain fungal and bacterial infections as demonstrated by patients with autoantibodies against IL-17A and IL-17F, or with inborn errors of IL-17 immunity.	INTRO
158	164	IL-17A	protein	IL-17A and its signaling is important in host defense against certain fungal and bacterial infections as demonstrated by patients with autoantibodies against IL-17A and IL-17F, or with inborn errors of IL-17 immunity.	INTRO
169	175	IL-17F	protein	IL-17A and its signaling is important in host defense against certain fungal and bacterial infections as demonstrated by patients with autoantibodies against IL-17A and IL-17F, or with inborn errors of IL-17 immunity.	INTRO
202	207	IL-17	protein_type	IL-17A and its signaling is important in host defense against certain fungal and bacterial infections as demonstrated by patients with autoantibodies against IL-17A and IL-17F, or with inborn errors of IL-17 immunity.	INTRO
39	45	IL-17A	protein	In addition to its physiological role, IL-17A is a key pathogenic factor in inflammatory and autoimmune diseases.	INTRO
61	71	antibodies	protein_type	In phase II and III clinical trials, neutralizing monoclonal antibodies against IL-17A (secukinumab and ixekizumab) or its receptor IL-17RA (brodalumab) are highly efficacious in treating moderate to severe plaque psoriasis and psoriatic arthritis.	INTRO
80	86	IL-17A	protein	In phase II and III clinical trials, neutralizing monoclonal antibodies against IL-17A (secukinumab and ixekizumab) or its receptor IL-17RA (brodalumab) are highly efficacious in treating moderate to severe plaque psoriasis and psoriatic arthritis.	INTRO
88	99	secukinumab	chemical	In phase II and III clinical trials, neutralizing monoclonal antibodies against IL-17A (secukinumab and ixekizumab) or its receptor IL-17RA (brodalumab) are highly efficacious in treating moderate to severe plaque psoriasis and psoriatic arthritis.	INTRO
104	114	ixekizumab	chemical	In phase II and III clinical trials, neutralizing monoclonal antibodies against IL-17A (secukinumab and ixekizumab) or its receptor IL-17RA (brodalumab) are highly efficacious in treating moderate to severe plaque psoriasis and psoriatic arthritis.	INTRO
123	131	receptor	protein_type	In phase II and III clinical trials, neutralizing monoclonal antibodies against IL-17A (secukinumab and ixekizumab) or its receptor IL-17RA (brodalumab) are highly efficacious in treating moderate to severe plaque psoriasis and psoriatic arthritis.	INTRO
132	139	IL-17RA	protein	In phase II and III clinical trials, neutralizing monoclonal antibodies against IL-17A (secukinumab and ixekizumab) or its receptor IL-17RA (brodalumab) are highly efficacious in treating moderate to severe plaque psoriasis and psoriatic arthritis.	INTRO
141	151	brodalumab	chemical	In phase II and III clinical trials, neutralizing monoclonal antibodies against IL-17A (secukinumab and ixekizumab) or its receptor IL-17RA (brodalumab) are highly efficacious in treating moderate to severe plaque psoriasis and psoriatic arthritis.	INTRO
0	11	Secukinumab	chemical	Secukinumab has been approved recently as a new psoriasis drug by the US Food and Drug Administration (Cosentyx™).	INTRO
103	112	Cosentyx™	chemical	Secukinumab has been approved recently as a new psoriasis drug by the US Food and Drug Administration (Cosentyx™).	INTRO
50	56	IL-17A	protein	In addition to psoriasis and psoriatic arthritis, IL-17A blockade has also shown preclinical and clinical efficacies in ankylosing spondylitis and rheumatoid arthritis.	INTRO
6	21	IL-17 cytokines	protein_type	Among IL-17 cytokines, IL-17A and IL-17F share the highest homology.	INTRO
23	29	IL-17A	protein	Among IL-17 cytokines, IL-17A and IL-17F share the highest homology.	INTRO
34	40	IL-17F	protein	Among IL-17 cytokines, IL-17A and IL-17F share the highest homology.	INTRO
24	32	covalent	protein_state	These polypeptides form covalent homodimers, and IL-17A and IL-17F also form an IL-17A/IL-17F hetereodimer.	INTRO
33	43	homodimers	oligomeric_state	These polypeptides form covalent homodimers, and IL-17A and IL-17F also form an IL-17A/IL-17F hetereodimer.	INTRO
49	55	IL-17A	protein	These polypeptides form covalent homodimers, and IL-17A and IL-17F also form an IL-17A/IL-17F hetereodimer.	INTRO
60	66	IL-17F	protein	These polypeptides form covalent homodimers, and IL-17A and IL-17F also form an IL-17A/IL-17F hetereodimer.	INTRO
80	93	IL-17A/IL-17F	complex_assembly	These polypeptides form covalent homodimers, and IL-17A and IL-17F also form an IL-17A/IL-17F hetereodimer.	INTRO
94	106	hetereodimer	oligomeric_state	These polypeptides form covalent homodimers, and IL-17A and IL-17F also form an IL-17A/IL-17F hetereodimer.	INTRO
0	10	Structures	evidence	Structures are known for apo IL-17F and its complex with IL-17RA, for apo IL-17A, its complex with an antibody Fab, and its complex with IL-17RA.	INTRO
25	28	apo	protein_state	Structures are known for apo IL-17F and its complex with IL-17RA, for apo IL-17A, its complex with an antibody Fab, and its complex with IL-17RA.	INTRO
29	35	IL-17F	protein	Structures are known for apo IL-17F and its complex with IL-17RA, for apo IL-17A, its complex with an antibody Fab, and its complex with IL-17RA.	INTRO
44	56	complex with	protein_state	Structures are known for apo IL-17F and its complex with IL-17RA, for apo IL-17A, its complex with an antibody Fab, and its complex with IL-17RA.	INTRO
57	64	IL-17RA	protein	Structures are known for apo IL-17F and its complex with IL-17RA, for apo IL-17A, its complex with an antibody Fab, and its complex with IL-17RA.	INTRO
70	73	apo	protein_state	Structures are known for apo IL-17F and its complex with IL-17RA, for apo IL-17A, its complex with an antibody Fab, and its complex with IL-17RA.	INTRO
74	80	IL-17A	protein	Structures are known for apo IL-17F and its complex with IL-17RA, for apo IL-17A, its complex with an antibody Fab, and its complex with IL-17RA.	INTRO
86	98	complex with	protein_state	Structures are known for apo IL-17F and its complex with IL-17RA, for apo IL-17A, its complex with an antibody Fab, and its complex with IL-17RA.	INTRO
102	110	antibody	protein_type	Structures are known for apo IL-17F and its complex with IL-17RA, for apo IL-17A, its complex with an antibody Fab, and its complex with IL-17RA.	INTRO
111	114	Fab	structure_element	Structures are known for apo IL-17F and its complex with IL-17RA, for apo IL-17A, its complex with an antibody Fab, and its complex with IL-17RA.	INTRO
124	136	complex with	protein_state	Structures are known for apo IL-17F and its complex with IL-17RA, for apo IL-17A, its complex with an antibody Fab, and its complex with IL-17RA.	INTRO
137	144	IL-17RA	protein	Structures are known for apo IL-17F and its complex with IL-17RA, for apo IL-17A, its complex with an antibody Fab, and its complex with IL-17RA.	INTRO
9	19	structures	evidence	In these structures, both IL-17A and IL-17F adopt a cysteine-knot fold with two intramolecular disulfides and two interchain disulfide bonds that covalently link two monomers.	INTRO
26	32	IL-17A	protein	In these structures, both IL-17A and IL-17F adopt a cysteine-knot fold with two intramolecular disulfides and two interchain disulfide bonds that covalently link two monomers.	INTRO
37	43	IL-17F	protein	In these structures, both IL-17A and IL-17F adopt a cysteine-knot fold with two intramolecular disulfides and two interchain disulfide bonds that covalently link two monomers.	INTRO
52	65	cysteine-knot	structure_element	In these structures, both IL-17A and IL-17F adopt a cysteine-knot fold with two intramolecular disulfides and two interchain disulfide bonds that covalently link two monomers.	INTRO
95	105	disulfides	ptm	In these structures, both IL-17A and IL-17F adopt a cysteine-knot fold with two intramolecular disulfides and two interchain disulfide bonds that covalently link two monomers.	INTRO
125	140	disulfide bonds	ptm	In these structures, both IL-17A and IL-17F adopt a cysteine-knot fold with two intramolecular disulfides and two interchain disulfide bonds that covalently link two monomers.	INTRO
166	174	monomers	oligomeric_state	In these structures, both IL-17A and IL-17F adopt a cysteine-knot fold with two intramolecular disulfides and two interchain disulfide bonds that covalently link two monomers.	INTRO
116	122	IL-17A	protein	There has been active research in identifying orally available chemical entities that would functionally antagonize IL-17A-mediated signaling.	INTRO
141	166	IL-17A/IL-17RA interfaces	site	Developing small molecules targeting protein-protein interactions is difficult with particular challenges associated with the large, shallow IL-17A/IL-17RA interfaces.	INTRO
6	13	IL-17RA	protein	Since IL-17RA is a shared receptor for at least IL-17A, IL-17F, IL-17A/IL-17F and IL-17E, we chose to seek IL-17A-specific inhibitors that may have more defined pharmacological responses than IL-17RA inhibitors.	INTRO
26	34	receptor	protein_type	Since IL-17RA is a shared receptor for at least IL-17A, IL-17F, IL-17A/IL-17F and IL-17E, we chose to seek IL-17A-specific inhibitors that may have more defined pharmacological responses than IL-17RA inhibitors.	INTRO
48	54	IL-17A	protein	Since IL-17RA is a shared receptor for at least IL-17A, IL-17F, IL-17A/IL-17F and IL-17E, we chose to seek IL-17A-specific inhibitors that may have more defined pharmacological responses than IL-17RA inhibitors.	INTRO
56	62	IL-17F	protein	Since IL-17RA is a shared receptor for at least IL-17A, IL-17F, IL-17A/IL-17F and IL-17E, we chose to seek IL-17A-specific inhibitors that may have more defined pharmacological responses than IL-17RA inhibitors.	INTRO
64	77	IL-17A/IL-17F	complex_assembly	Since IL-17RA is a shared receptor for at least IL-17A, IL-17F, IL-17A/IL-17F and IL-17E, we chose to seek IL-17A-specific inhibitors that may have more defined pharmacological responses than IL-17RA inhibitors.	INTRO
82	88	IL-17E	protein	Since IL-17RA is a shared receptor for at least IL-17A, IL-17F, IL-17A/IL-17F and IL-17E, we chose to seek IL-17A-specific inhibitors that may have more defined pharmacological responses than IL-17RA inhibitors.	INTRO
107	113	IL-17A	protein	Since IL-17RA is a shared receptor for at least IL-17A, IL-17F, IL-17A/IL-17F and IL-17E, we chose to seek IL-17A-specific inhibitors that may have more defined pharmacological responses than IL-17RA inhibitors.	INTRO
192	199	IL-17RA	protein	Since IL-17RA is a shared receptor for at least IL-17A, IL-17F, IL-17A/IL-17F and IL-17E, we chose to seek IL-17A-specific inhibitors that may have more defined pharmacological responses than IL-17RA inhibitors.	INTRO
39	78	high affinity IL-17A peptide antagonist	chemical	Our efforts resulted in discovery of a high affinity IL-17A peptide antagonist (HAP), which we attempted to increase the functional production and pharmacokinetics after fusing HAP to antibodies for evaluation as a bispecific therapeutic in animal studies.	INTRO
80	83	HAP	chemical	Our efforts resulted in discovery of a high affinity IL-17A peptide antagonist (HAP), which we attempted to increase the functional production and pharmacokinetics after fusing HAP to antibodies for evaluation as a bispecific therapeutic in animal studies.	INTRO
170	176	fusing	experimental_method	Our efforts resulted in discovery of a high affinity IL-17A peptide antagonist (HAP), which we attempted to increase the functional production and pharmacokinetics after fusing HAP to antibodies for evaluation as a bispecific therapeutic in animal studies.	INTRO
177	180	HAP	chemical	Our efforts resulted in discovery of a high affinity IL-17A peptide antagonist (HAP), which we attempted to increase the functional production and pharmacokinetics after fusing HAP to antibodies for evaluation as a bispecific therapeutic in animal studies.	INTRO
184	194	antibodies	protein_type	Our efforts resulted in discovery of a high affinity IL-17A peptide antagonist (HAP), which we attempted to increase the functional production and pharmacokinetics after fusing HAP to antibodies for evaluation as a bispecific therapeutic in animal studies.	INTRO
63	71	uncapped	protein_state	Unfortunately, this past work revealed stability issues of the uncapped HAP in cell culture Here, we provide the details of the discovery and optimization that led to HAP and report the complex structure of IL-17A with HAP, which provides structure based rationalization of peptide optimization and structure activity relationship (SAR).	INTRO
72	75	HAP	chemical	Unfortunately, this past work revealed stability issues of the uncapped HAP in cell culture Here, we provide the details of the discovery and optimization that led to HAP and report the complex structure of IL-17A with HAP, which provides structure based rationalization of peptide optimization and structure activity relationship (SAR).	INTRO
167	170	HAP	chemical	Unfortunately, this past work revealed stability issues of the uncapped HAP in cell culture Here, we provide the details of the discovery and optimization that led to HAP and report the complex structure of IL-17A with HAP, which provides structure based rationalization of peptide optimization and structure activity relationship (SAR).	INTRO
186	203	complex structure	evidence	Unfortunately, this past work revealed stability issues of the uncapped HAP in cell culture Here, we provide the details of the discovery and optimization that led to HAP and report the complex structure of IL-17A with HAP, which provides structure based rationalization of peptide optimization and structure activity relationship (SAR).	INTRO
207	213	IL-17A	protein	Unfortunately, this past work revealed stability issues of the uncapped HAP in cell culture Here, we provide the details of the discovery and optimization that led to HAP and report the complex structure of IL-17A with HAP, which provides structure based rationalization of peptide optimization and structure activity relationship (SAR).	INTRO
219	222	HAP	chemical	Unfortunately, this past work revealed stability issues of the uncapped HAP in cell culture Here, we provide the details of the discovery and optimization that led to HAP and report the complex structure of IL-17A with HAP, which provides structure based rationalization of peptide optimization and structure activity relationship (SAR).	INTRO
274	294	peptide optimization	experimental_method	Unfortunately, this past work revealed stability issues of the uncapped HAP in cell culture Here, we provide the details of the discovery and optimization that led to HAP and report the complex structure of IL-17A with HAP, which provides structure based rationalization of peptide optimization and structure activity relationship (SAR).	INTRO
299	330	structure activity relationship	experimental_method	Unfortunately, this past work revealed stability issues of the uncapped HAP in cell culture Here, we provide the details of the discovery and optimization that led to HAP and report the complex structure of IL-17A with HAP, which provides structure based rationalization of peptide optimization and structure activity relationship (SAR).	INTRO
332	335	SAR	experimental_method	Unfortunately, this past work revealed stability issues of the uncapped HAP in cell culture Here, we provide the details of the discovery and optimization that led to HAP and report the complex structure of IL-17A with HAP, which provides structure based rationalization of peptide optimization and structure activity relationship (SAR).	INTRO
18	24	IL-17A	protein	Identification of IL-17A peptide inhibitors	RESULTS
33	38	human	species	Peptides specifically binding to human IL-17A were identified from phage panning using cyclic and linear peptide libraries (Supplementary Figure S1).	RESULTS
39	45	IL-17A	protein	Peptides specifically binding to human IL-17A were identified from phage panning using cyclic and linear peptide libraries (Supplementary Figure S1).	RESULTS
67	80	phage panning	experimental_method	Peptides specifically binding to human IL-17A were identified from phage panning using cyclic and linear peptide libraries (Supplementary Figure S1).	RESULTS
87	122	cyclic and linear peptide libraries	experimental_method	Peptides specifically binding to human IL-17A were identified from phage panning using cyclic and linear peptide libraries (Supplementary Figure S1).	RESULTS
0	20	Positive phage pools	experimental_method	Positive phage pools were then sub-cloned into a maltose-binding protein (MBP) fusion system.	RESULTS
31	41	sub-cloned	experimental_method	Positive phage pools were then sub-cloned into a maltose-binding protein (MBP) fusion system.	RESULTS
49	92	maltose-binding protein (MBP) fusion system	experimental_method	Positive phage pools were then sub-cloned into a maltose-binding protein (MBP) fusion system.	RESULTS
104	137	enzyme-linked immunosorbent assay	experimental_method	Single clones were isolated and sub-cultured in growth medium, and culture supernatants were used in an enzyme-linked immunosorbent assay (ELISA) to identify specific IL-17A-binding clones.	RESULTS
139	144	ELISA	experimental_method	Single clones were isolated and sub-cultured in growth medium, and culture supernatants were used in an enzyme-linked immunosorbent assay (ELISA) to identify specific IL-17A-binding clones.	RESULTS
167	173	IL-17A	protein	Single clones were isolated and sub-cultured in growth medium, and culture supernatants were used in an enzyme-linked immunosorbent assay (ELISA) to identify specific IL-17A-binding clones.	RESULTS
71	83	biotinylated	protein_state	The positive binding supernatants were tested for the ability to block biotinylated IL-17A signaling through IL-17RA in an IL-17A/IL-17RA competition ELISA assay where unlabeled IL-17A was used as positive control to inhibit biotinylated IL-17A binding.	RESULTS
84	90	IL-17A	protein	The positive binding supernatants were tested for the ability to block biotinylated IL-17A signaling through IL-17RA in an IL-17A/IL-17RA competition ELISA assay where unlabeled IL-17A was used as positive control to inhibit biotinylated IL-17A binding.	RESULTS
109	116	IL-17RA	protein	The positive binding supernatants were tested for the ability to block biotinylated IL-17A signaling through IL-17RA in an IL-17A/IL-17RA competition ELISA assay where unlabeled IL-17A was used as positive control to inhibit biotinylated IL-17A binding.	RESULTS
123	137	IL-17A/IL-17RA	complex_assembly	The positive binding supernatants were tested for the ability to block biotinylated IL-17A signaling through IL-17RA in an IL-17A/IL-17RA competition ELISA assay where unlabeled IL-17A was used as positive control to inhibit biotinylated IL-17A binding.	RESULTS
138	161	competition ELISA assay	experimental_method	The positive binding supernatants were tested for the ability to block biotinylated IL-17A signaling through IL-17RA in an IL-17A/IL-17RA competition ELISA assay where unlabeled IL-17A was used as positive control to inhibit biotinylated IL-17A binding.	RESULTS
178	184	IL-17A	protein	The positive binding supernatants were tested for the ability to block biotinylated IL-17A signaling through IL-17RA in an IL-17A/IL-17RA competition ELISA assay where unlabeled IL-17A was used as positive control to inhibit biotinylated IL-17A binding.	RESULTS
225	237	biotinylated	protein_state	The positive binding supernatants were tested for the ability to block biotinylated IL-17A signaling through IL-17RA in an IL-17A/IL-17RA competition ELISA assay where unlabeled IL-17A was used as positive control to inhibit biotinylated IL-17A binding.	RESULTS
238	244	IL-17A	protein	The positive binding supernatants were tested for the ability to block biotinylated IL-17A signaling through IL-17RA in an IL-17A/IL-17RA competition ELISA assay where unlabeled IL-17A was used as positive control to inhibit biotinylated IL-17A binding.	RESULTS
59	65	IL-17A	protein	Approximately 10% of the clones that specifically bound to IL-17A also prevented the cytokine from binding to IL-17RA.	RESULTS
85	93	cytokine	protein_type	Approximately 10% of the clones that specifically bound to IL-17A also prevented the cytokine from binding to IL-17RA.	RESULTS
110	117	IL-17RA	protein	Approximately 10% of the clones that specifically bound to IL-17A also prevented the cytokine from binding to IL-17RA.	RESULTS
26	38	phage clones	experimental_method	Sequences identified from phage clones were chemically synthesized (Supplementary Table 1) and tested for inhibition of IL-17A binding to IL-17RA (Table 1).	RESULTS
44	66	chemically synthesized	experimental_method	Sequences identified from phage clones were chemically synthesized (Supplementary Table 1) and tested for inhibition of IL-17A binding to IL-17RA (Table 1).	RESULTS
120	126	IL-17A	protein	Sequences identified from phage clones were chemically synthesized (Supplementary Table 1) and tested for inhibition of IL-17A binding to IL-17RA (Table 1).	RESULTS
138	145	IL-17RA	protein	Sequences identified from phage clones were chemically synthesized (Supplementary Table 1) and tested for inhibition of IL-17A binding to IL-17RA (Table 1).	RESULTS
16	25	peptide 1	chemical	A 15-mer linear peptide 1 was shown to block IL-17A/IL-17RA binding with an IC50 of 80 nM in the competition ELISA assay (Table 1).	RESULTS
45	59	IL-17A/IL-17RA	complex_assembly	A 15-mer linear peptide 1 was shown to block IL-17A/IL-17RA binding with an IC50 of 80 nM in the competition ELISA assay (Table 1).	RESULTS
76	80	IC50	evidence	A 15-mer linear peptide 1 was shown to block IL-17A/IL-17RA binding with an IC50 of 80 nM in the competition ELISA assay (Table 1).	RESULTS
97	120	competition ELISA assay	experimental_method	A 15-mer linear peptide 1 was shown to block IL-17A/IL-17RA binding with an IC50 of 80 nM in the competition ELISA assay (Table 1).	RESULTS
34	61	cell-based functional assay	experimental_method	This peptide was then tested in a cell-based functional assay wherein production of GRO-α in BJ human fibroblast cells was measured as a function of IL-17A stimulation using 1 ng/ml IL-17A.	RESULTS
84	89	GRO-α	protein	This peptide was then tested in a cell-based functional assay wherein production of GRO-α in BJ human fibroblast cells was measured as a function of IL-17A stimulation using 1 ng/ml IL-17A.	RESULTS
96	101	human	species	This peptide was then tested in a cell-based functional assay wherein production of GRO-α in BJ human fibroblast cells was measured as a function of IL-17A stimulation using 1 ng/ml IL-17A.	RESULTS
149	155	IL-17A	protein	This peptide was then tested in a cell-based functional assay wherein production of GRO-α in BJ human fibroblast cells was measured as a function of IL-17A stimulation using 1 ng/ml IL-17A.	RESULTS
182	188	IL-17A	protein	This peptide was then tested in a cell-based functional assay wherein production of GRO-α in BJ human fibroblast cells was measured as a function of IL-17A stimulation using 1 ng/ml IL-17A.	RESULTS
0	9	Peptide 1	chemical	Peptide 1 was found to be active in this functional assay with an IC50 of 370 nM.	RESULTS
41	57	functional assay	experimental_method	Peptide 1 was found to be active in this functional assay with an IC50 of 370 nM.	RESULTS
66	70	IC50	evidence	Peptide 1 was found to be active in this functional assay with an IC50 of 370 nM.	RESULTS
16	22	IL-17A	protein	Optimization of IL-17A peptide inhibitors	RESULTS
2	5	SAR	experimental_method	A SAR campaign was undertaken to improve the potency of peptide 1.	RESULTS
56	65	peptide 1	chemical	A SAR campaign was undertaken to improve the potency of peptide 1.	RESULTS
3	15	alanine scan	experimental_method	An alanine scan of peptide 2, an analogue of 1 with a lysine to arginine substitution at position 14, was initiated.	RESULTS
19	28	peptide 2	chemical	An alanine scan of peptide 2, an analogue of 1 with a lysine to arginine substitution at position 14, was initiated.	RESULTS
45	46	1	chemical	An alanine scan of peptide 2, an analogue of 1 with a lysine to arginine substitution at position 14, was initiated.	RESULTS
54	60	lysine	residue_name	An alanine scan of peptide 2, an analogue of 1 with a lysine to arginine substitution at position 14, was initiated.	RESULTS
64	72	arginine	residue_name	An alanine scan of peptide 2, an analogue of 1 with a lysine to arginine substitution at position 14, was initiated.	RESULTS
73	85	substitution	experimental_method	An alanine scan of peptide 2, an analogue of 1 with a lysine to arginine substitution at position 14, was initiated.	RESULTS
98	100	14	residue_number	An alanine scan of peptide 2, an analogue of 1 with a lysine to arginine substitution at position 14, was initiated.	RESULTS
5	12	alanine	residue_name	When alanine was already present (positions 7 and 15), substitution was made with lysine (Table 1, peptides 3–17).	RESULTS
44	45	7	residue_number	When alanine was already present (positions 7 and 15), substitution was made with lysine (Table 1, peptides 3–17).	RESULTS
50	52	15	residue_number	When alanine was already present (positions 7 and 15), substitution was made with lysine (Table 1, peptides 3–17).	RESULTS
55	67	substitution	experimental_method	When alanine was already present (positions 7 and 15), substitution was made with lysine (Table 1, peptides 3–17).	RESULTS
82	88	lysine	residue_name	When alanine was already present (positions 7 and 15), substitution was made with lysine (Table 1, peptides 3–17).	RESULTS
99	112	peptides 3–17	chemical	When alanine was already present (positions 7 and 15), substitution was made with lysine (Table 1, peptides 3–17).	RESULTS
10	11	1	residue_number	Positions 1, 2, 4, 5, 7, 14 and 15 were shown to be amenable to substitution without significant loss (less than 3-fold) of binding affinity as measured by the IL-17A/IL-17RA competition ELISA.	RESULTS
13	14	2	residue_number	Positions 1, 2, 4, 5, 7, 14 and 15 were shown to be amenable to substitution without significant loss (less than 3-fold) of binding affinity as measured by the IL-17A/IL-17RA competition ELISA.	RESULTS
16	17	4	residue_number	Positions 1, 2, 4, 5, 7, 14 and 15 were shown to be amenable to substitution without significant loss (less than 3-fold) of binding affinity as measured by the IL-17A/IL-17RA competition ELISA.	RESULTS
19	20	5	residue_number	Positions 1, 2, 4, 5, 7, 14 and 15 were shown to be amenable to substitution without significant loss (less than 3-fold) of binding affinity as measured by the IL-17A/IL-17RA competition ELISA.	RESULTS
22	23	7	residue_number	Positions 1, 2, 4, 5, 7, 14 and 15 were shown to be amenable to substitution without significant loss (less than 3-fold) of binding affinity as measured by the IL-17A/IL-17RA competition ELISA.	RESULTS
25	27	14	residue_number	Positions 1, 2, 4, 5, 7, 14 and 15 were shown to be amenable to substitution without significant loss (less than 3-fold) of binding affinity as measured by the IL-17A/IL-17RA competition ELISA.	RESULTS
32	34	15	residue_number	Positions 1, 2, 4, 5, 7, 14 and 15 were shown to be amenable to substitution without significant loss (less than 3-fold) of binding affinity as measured by the IL-17A/IL-17RA competition ELISA.	RESULTS
124	140	binding affinity	evidence	Positions 1, 2, 4, 5, 7, 14 and 15 were shown to be amenable to substitution without significant loss (less than 3-fold) of binding affinity as measured by the IL-17A/IL-17RA competition ELISA.	RESULTS
160	174	IL-17A/IL-17RA	complex_assembly	Positions 1, 2, 4, 5, 7, 14 and 15 were shown to be amenable to substitution without significant loss (less than 3-fold) of binding affinity as measured by the IL-17A/IL-17RA competition ELISA.	RESULTS
175	192	competition ELISA	experimental_method	Positions 1, 2, 4, 5, 7, 14 and 15 were shown to be amenable to substitution without significant loss (less than 3-fold) of binding affinity as measured by the IL-17A/IL-17RA competition ELISA.	RESULTS
27	28	5	residue_number	In particular, at position 5 (13), substitution of methionine with alanine resulted in a seven fold improvement in potency (80 nM versus 11 nM respectively).	RESULTS
30	32	13	chemical	In particular, at position 5 (13), substitution of methionine with alanine resulted in a seven fold improvement in potency (80 nM versus 11 nM respectively).	RESULTS
35	47	substitution	experimental_method	In particular, at position 5 (13), substitution of methionine with alanine resulted in a seven fold improvement in potency (80 nM versus 11 nM respectively).	RESULTS
51	61	methionine	residue_name	In particular, at position 5 (13), substitution of methionine with alanine resulted in a seven fold improvement in potency (80 nM versus 11 nM respectively).	RESULTS
67	74	alanine	residue_name	In particular, at position 5 (13), substitution of methionine with alanine resulted in a seven fold improvement in potency (80 nM versus 11 nM respectively).	RESULTS
44	56	substitution	experimental_method	In order to rapidly evaluate the effects of substitution of natural amino acids at tolerant positions identified by the alanine scan, the lead sequence was subjected to site-specific saturation mutagenesis using MBP.	RESULTS
120	132	alanine scan	experimental_method	In order to rapidly evaluate the effects of substitution of natural amino acids at tolerant positions identified by the alanine scan, the lead sequence was subjected to site-specific saturation mutagenesis using MBP.	RESULTS
169	205	site-specific saturation mutagenesis	experimental_method	In order to rapidly evaluate the effects of substitution of natural amino acids at tolerant positions identified by the alanine scan, the lead sequence was subjected to site-specific saturation mutagenesis using MBP.	RESULTS
212	215	MBP	experimental_method	In order to rapidly evaluate the effects of substitution of natural amino acids at tolerant positions identified by the alanine scan, the lead sequence was subjected to site-specific saturation mutagenesis using MBP.	RESULTS
46	58	alanine scan	experimental_method	Each of the seven positions identified by the alanine scan was individually modified while keeping the rest of the sequence constant.	RESULTS
27	28	2	residue_number	Modifications at positions 2 and 14 were shown to display improvement in binding affinity (data not shown).	RESULTS
33	35	14	residue_number	Modifications at positions 2 and 14 were shown to display improvement in binding affinity (data not shown).	RESULTS
73	89	binding affinity	evidence	Modifications at positions 2 and 14 were shown to display improvement in binding affinity (data not shown).	RESULTS
25	40	point mutations	experimental_method	Peptides with beneficial point mutations at positions 2, 5, and 14 were synthesized and evaluated in the competition ELISA (Table 1).	RESULTS
54	55	2	residue_number	Peptides with beneficial point mutations at positions 2, 5, and 14 were synthesized and evaluated in the competition ELISA (Table 1).	RESULTS
57	58	5	residue_number	Peptides with beneficial point mutations at positions 2, 5, and 14 were synthesized and evaluated in the competition ELISA (Table 1).	RESULTS
64	66	14	residue_number	Peptides with beneficial point mutations at positions 2, 5, and 14 were synthesized and evaluated in the competition ELISA (Table 1).	RESULTS
72	83	synthesized	experimental_method	Peptides with beneficial point mutations at positions 2, 5, and 14 were synthesized and evaluated in the competition ELISA (Table 1).	RESULTS
105	122	competition ELISA	experimental_method	Peptides with beneficial point mutations at positions 2, 5, and 14 were synthesized and evaluated in the competition ELISA (Table 1).	RESULTS
20	23	V2H	mutant	Two of the changes, V2H (18) or V2T (21) displayed improved binding in the competition ELISA.	RESULTS
25	27	18	chemical	Two of the changes, V2H (18) or V2T (21) displayed improved binding in the competition ELISA.	RESULTS
32	35	V2T	mutant	Two of the changes, V2H (18) or V2T (21) displayed improved binding in the competition ELISA.	RESULTS
37	39	21	chemical	Two of the changes, V2H (18) or V2T (21) displayed improved binding in the competition ELISA.	RESULTS
75	92	competition ELISA	experimental_method	Two of the changes, V2H (18) or V2T (21) displayed improved binding in the competition ELISA.	RESULTS
10	21	replacement	experimental_method	Since the replacement of methionine at position 5 with alanine was beneficial, the additional hydrophobic amino acids isoleucine (24), leucine (25) and valine (26) were evaluated and an additional two-three fold improvement in binding was observed for the valine and isoleucine replacements in comparison with alanine.	RESULTS
25	35	methionine	residue_name	Since the replacement of methionine at position 5 with alanine was beneficial, the additional hydrophobic amino acids isoleucine (24), leucine (25) and valine (26) were evaluated and an additional two-three fold improvement in binding was observed for the valine and isoleucine replacements in comparison with alanine.	RESULTS
48	49	5	residue_number	Since the replacement of methionine at position 5 with alanine was beneficial, the additional hydrophobic amino acids isoleucine (24), leucine (25) and valine (26) were evaluated and an additional two-three fold improvement in binding was observed for the valine and isoleucine replacements in comparison with alanine.	RESULTS
55	62	alanine	residue_name	Since the replacement of methionine at position 5 with alanine was beneficial, the additional hydrophobic amino acids isoleucine (24), leucine (25) and valine (26) were evaluated and an additional two-three fold improvement in binding was observed for the valine and isoleucine replacements in comparison with alanine.	RESULTS
118	128	isoleucine	residue_name	Since the replacement of methionine at position 5 with alanine was beneficial, the additional hydrophobic amino acids isoleucine (24), leucine (25) and valine (26) were evaluated and an additional two-three fold improvement in binding was observed for the valine and isoleucine replacements in comparison with alanine.	RESULTS
130	132	24	chemical	Since the replacement of methionine at position 5 with alanine was beneficial, the additional hydrophobic amino acids isoleucine (24), leucine (25) and valine (26) were evaluated and an additional two-three fold improvement in binding was observed for the valine and isoleucine replacements in comparison with alanine.	RESULTS
135	142	leucine	residue_name	Since the replacement of methionine at position 5 with alanine was beneficial, the additional hydrophobic amino acids isoleucine (24), leucine (25) and valine (26) were evaluated and an additional two-three fold improvement in binding was observed for the valine and isoleucine replacements in comparison with alanine.	RESULTS
144	146	25	chemical	Since the replacement of methionine at position 5 with alanine was beneficial, the additional hydrophobic amino acids isoleucine (24), leucine (25) and valine (26) were evaluated and an additional two-three fold improvement in binding was observed for the valine and isoleucine replacements in comparison with alanine.	RESULTS
152	158	valine	residue_name	Since the replacement of methionine at position 5 with alanine was beneficial, the additional hydrophobic amino acids isoleucine (24), leucine (25) and valine (26) were evaluated and an additional two-three fold improvement in binding was observed for the valine and isoleucine replacements in comparison with alanine.	RESULTS
160	162	26	chemical	Since the replacement of methionine at position 5 with alanine was beneficial, the additional hydrophobic amino acids isoleucine (24), leucine (25) and valine (26) were evaluated and an additional two-three fold improvement in binding was observed for the valine and isoleucine replacements in comparison with alanine.	RESULTS
256	262	valine	residue_name	Since the replacement of methionine at position 5 with alanine was beneficial, the additional hydrophobic amino acids isoleucine (24), leucine (25) and valine (26) were evaluated and an additional two-three fold improvement in binding was observed for the valine and isoleucine replacements in comparison with alanine.	RESULTS
267	277	isoleucine	residue_name	Since the replacement of methionine at position 5 with alanine was beneficial, the additional hydrophobic amino acids isoleucine (24), leucine (25) and valine (26) were evaluated and an additional two-three fold improvement in binding was observed for the valine and isoleucine replacements in comparison with alanine.	RESULTS
278	290	replacements	experimental_method	Since the replacement of methionine at position 5 with alanine was beneficial, the additional hydrophobic amino acids isoleucine (24), leucine (25) and valine (26) were evaluated and an additional two-three fold improvement in binding was observed for the valine and isoleucine replacements in comparison with alanine.	RESULTS
310	317	alanine	residue_name	Since the replacement of methionine at position 5 with alanine was beneficial, the additional hydrophobic amino acids isoleucine (24), leucine (25) and valine (26) were evaluated and an additional two-three fold improvement in binding was observed for the valine and isoleucine replacements in comparison with alanine.	RESULTS
0	12	Introduction	experimental_method	Introduction of a methionine (27) or a carboxamide (28 and 29) at position 14 was shown to improve the binding affinity of the lead peptide.	RESULTS
18	28	methionine	residue_name	Introduction of a methionine (27) or a carboxamide (28 and 29) at position 14 was shown to improve the binding affinity of the lead peptide.	RESULTS
30	32	27	chemical	Introduction of a methionine (27) or a carboxamide (28 and 29) at position 14 was shown to improve the binding affinity of the lead peptide.	RESULTS
39	50	carboxamide	chemical	Introduction of a methionine (27) or a carboxamide (28 and 29) at position 14 was shown to improve the binding affinity of the lead peptide.	RESULTS
52	54	28	chemical	Introduction of a methionine (27) or a carboxamide (28 and 29) at position 14 was shown to improve the binding affinity of the lead peptide.	RESULTS
59	61	29	chemical	Introduction of a methionine (27) or a carboxamide (28 and 29) at position 14 was shown to improve the binding affinity of the lead peptide.	RESULTS
75	77	14	residue_number	Introduction of a methionine (27) or a carboxamide (28 and 29) at position 14 was shown to improve the binding affinity of the lead peptide.	RESULTS
103	119	binding affinity	evidence	Introduction of a methionine (27) or a carboxamide (28 and 29) at position 14 was shown to improve the binding affinity of the lead peptide.	RESULTS
60	78	binding affinities	evidence	In general, there was good agreement between the respective binding affinities of the synthesized peptides and their MBP fusion counterparts, except for substitution of valine at position 2 to a tryptophan (22), which resulted in a fivefold loss of affinity, for the free peptide when compared with the MBP fusion.	RESULTS
117	127	MBP fusion	experimental_method	In general, there was good agreement between the respective binding affinities of the synthesized peptides and their MBP fusion counterparts, except for substitution of valine at position 2 to a tryptophan (22), which resulted in a fivefold loss of affinity, for the free peptide when compared with the MBP fusion.	RESULTS
153	165	substitution	experimental_method	In general, there was good agreement between the respective binding affinities of the synthesized peptides and their MBP fusion counterparts, except for substitution of valine at position 2 to a tryptophan (22), which resulted in a fivefold loss of affinity, for the free peptide when compared with the MBP fusion.	RESULTS
169	175	valine	residue_name	In general, there was good agreement between the respective binding affinities of the synthesized peptides and their MBP fusion counterparts, except for substitution of valine at position 2 to a tryptophan (22), which resulted in a fivefold loss of affinity, for the free peptide when compared with the MBP fusion.	RESULTS
188	189	2	residue_number	In general, there was good agreement between the respective binding affinities of the synthesized peptides and their MBP fusion counterparts, except for substitution of valine at position 2 to a tryptophan (22), which resulted in a fivefold loss of affinity, for the free peptide when compared with the MBP fusion.	RESULTS
195	205	tryptophan	residue_name	In general, there was good agreement between the respective binding affinities of the synthesized peptides and their MBP fusion counterparts, except for substitution of valine at position 2 to a tryptophan (22), which resulted in a fivefold loss of affinity, for the free peptide when compared with the MBP fusion.	RESULTS
207	209	22	chemical	In general, there was good agreement between the respective binding affinities of the synthesized peptides and their MBP fusion counterparts, except for substitution of valine at position 2 to a tryptophan (22), which resulted in a fivefold loss of affinity, for the free peptide when compared with the MBP fusion.	RESULTS
249	257	affinity	evidence	In general, there was good agreement between the respective binding affinities of the synthesized peptides and their MBP fusion counterparts, except for substitution of valine at position 2 to a tryptophan (22), which resulted in a fivefold loss of affinity, for the free peptide when compared with the MBP fusion.	RESULTS
303	313	MBP fusion	experimental_method	In general, there was good agreement between the respective binding affinities of the synthesized peptides and their MBP fusion counterparts, except for substitution of valine at position 2 to a tryptophan (22), which resulted in a fivefold loss of affinity, for the free peptide when compared with the MBP fusion.	RESULTS
52	55	SAR	experimental_method	Combining the key amino-acid residues identified by SAR into a single peptide sequence resulted in peptide 30, named high affinity peptide (HAP), that was found to inhibit IL-17A signaling in a BJ human fibroblast cell assay with an IC50 of 17 nM, a more than 20-fold improvement over the phage peptide 1 (Table 2 and Supplementary Figure S2).	RESULTS
99	109	peptide 30	chemical	Combining the key amino-acid residues identified by SAR into a single peptide sequence resulted in peptide 30, named high affinity peptide (HAP), that was found to inhibit IL-17A signaling in a BJ human fibroblast cell assay with an IC50 of 17 nM, a more than 20-fold improvement over the phage peptide 1 (Table 2 and Supplementary Figure S2).	RESULTS
117	138	high affinity peptide	chemical	Combining the key amino-acid residues identified by SAR into a single peptide sequence resulted in peptide 30, named high affinity peptide (HAP), that was found to inhibit IL-17A signaling in a BJ human fibroblast cell assay with an IC50 of 17 nM, a more than 20-fold improvement over the phage peptide 1 (Table 2 and Supplementary Figure S2).	RESULTS
140	143	HAP	chemical	Combining the key amino-acid residues identified by SAR into a single peptide sequence resulted in peptide 30, named high affinity peptide (HAP), that was found to inhibit IL-17A signaling in a BJ human fibroblast cell assay with an IC50 of 17 nM, a more than 20-fold improvement over the phage peptide 1 (Table 2 and Supplementary Figure S2).	RESULTS
172	178	IL-17A	protein	Combining the key amino-acid residues identified by SAR into a single peptide sequence resulted in peptide 30, named high affinity peptide (HAP), that was found to inhibit IL-17A signaling in a BJ human fibroblast cell assay with an IC50 of 17 nM, a more than 20-fold improvement over the phage peptide 1 (Table 2 and Supplementary Figure S2).	RESULTS
197	202	human	species	Combining the key amino-acid residues identified by SAR into a single peptide sequence resulted in peptide 30, named high affinity peptide (HAP), that was found to inhibit IL-17A signaling in a BJ human fibroblast cell assay with an IC50 of 17 nM, a more than 20-fold improvement over the phage peptide 1 (Table 2 and Supplementary Figure S2).	RESULTS
233	237	IC50	evidence	Combining the key amino-acid residues identified by SAR into a single peptide sequence resulted in peptide 30, named high affinity peptide (HAP), that was found to inhibit IL-17A signaling in a BJ human fibroblast cell assay with an IC50 of 17 nM, a more than 20-fold improvement over the phage peptide 1 (Table 2 and Supplementary Figure S2).	RESULTS
289	294	phage	experimental_method	Combining the key amino-acid residues identified by SAR into a single peptide sequence resulted in peptide 30, named high affinity peptide (HAP), that was found to inhibit IL-17A signaling in a BJ human fibroblast cell assay with an IC50 of 17 nM, a more than 20-fold improvement over the phage peptide 1 (Table 2 and Supplementary Figure S2).	RESULTS
295	304	peptide 1	chemical	Combining the key amino-acid residues identified by SAR into a single peptide sequence resulted in peptide 30, named high affinity peptide (HAP), that was found to inhibit IL-17A signaling in a BJ human fibroblast cell assay with an IC50 of 17 nM, a more than 20-fold improvement over the phage peptide 1 (Table 2 and Supplementary Figure S2).	RESULTS
78	81	HAP	chemical	We also examined the effect of removing the acetyl group at the N-terminus of HAP (which is present in all the peptides made, see Supplementary Material).	RESULTS
4	13	un-capped	protein_state	The un-capped peptide (31) had an IC50 of 420 nM in the cell-based assay.	RESULTS
14	26	peptide (31)	chemical	The un-capped peptide (31) had an IC50 of 420 nM in the cell-based assay.	RESULTS
34	38	IC50	evidence	The un-capped peptide (31) had an IC50 of 420 nM in the cell-based assay.	RESULTS
56	72	cell-based assay	experimental_method	The un-capped peptide (31) had an IC50 of 420 nM in the cell-based assay.	RESULTS
33	35	31	chemical	The loss of cellular activity of 31 was most likely due to the degradation of the N-terminus of 31, since peptide 31 was shown to be able to bind to IL-17A with similar affinity as HAP itself.	RESULTS
96	98	31	chemical	The loss of cellular activity of 31 was most likely due to the degradation of the N-terminus of 31, since peptide 31 was shown to be able to bind to IL-17A with similar affinity as HAP itself.	RESULTS
114	116	31	chemical	The loss of cellular activity of 31 was most likely due to the degradation of the N-terminus of 31, since peptide 31 was shown to be able to bind to IL-17A with similar affinity as HAP itself.	RESULTS
149	155	IL-17A	protein	The loss of cellular activity of 31 was most likely due to the degradation of the N-terminus of 31, since peptide 31 was shown to be able to bind to IL-17A with similar affinity as HAP itself.	RESULTS
181	184	HAP	chemical	The loss of cellular activity of 31 was most likely due to the degradation of the N-terminus of 31, since peptide 31 was shown to be able to bind to IL-17A with similar affinity as HAP itself.	RESULTS
52	68	antibody fusions	experimental_method	Furthermore, our previous work had reported that in antibody fusions the uncapped peptide was degraded under cell assay conditions with removal of the first 1-3 residues to inactive products with the same N-terminal sequences as peptides 32–34.	RESULTS
73	81	uncapped	protein_state	Furthermore, our previous work had reported that in antibody fusions the uncapped peptide was degraded under cell assay conditions with removal of the first 1-3 residues to inactive products with the same N-terminal sequences as peptides 32–34.	RESULTS
82	89	peptide	chemical	Furthermore, our previous work had reported that in antibody fusions the uncapped peptide was degraded under cell assay conditions with removal of the first 1-3 residues to inactive products with the same N-terminal sequences as peptides 32–34.	RESULTS
136	146	removal of	experimental_method	Furthermore, our previous work had reported that in antibody fusions the uncapped peptide was degraded under cell assay conditions with removal of the first 1-3 residues to inactive products with the same N-terminal sequences as peptides 32–34.	RESULTS
151	169	first 1-3 residues	residue_range	Furthermore, our previous work had reported that in antibody fusions the uncapped peptide was degraded under cell assay conditions with removal of the first 1-3 residues to inactive products with the same N-terminal sequences as peptides 32–34.	RESULTS
229	243	peptides 32–34	chemical	Furthermore, our previous work had reported that in antibody fusions the uncapped peptide was degraded under cell assay conditions with removal of the first 1-3 residues to inactive products with the same N-terminal sequences as peptides 32–34.	RESULTS
14	19	32–34	chemical	In this work, 32–34 are capped by protective acetyl group and reflect the same inactivity as reported.	RESULTS
24	30	capped	protein_state	In this work, 32–34 are capped by protective acetyl group and reflect the same inactivity as reported.	RESULTS
11	22	truncations	experimental_method	C-terminal truncations showed a more gradual reduction in activity (35–37; Table 2).	RESULTS
68	73	35–37	chemical	C-terminal truncations showed a more gradual reduction in activity (35–37; Table 2).	RESULTS
6	17	deletion of	experimental_method	After deletion of three amino acids from the C-terminal end (37), the peptide is no longer active.	RESULTS
18	35	three amino acids	residue_range	After deletion of three amino acids from the C-terminal end (37), the peptide is no longer active.	RESULTS
61	63	37	chemical	After deletion of three amino acids from the C-terminal end (37), the peptide is no longer active.	RESULTS
16	19	HAP	chemical	Dimerization of HAP can further increase its potency	RESULTS
27	33	IL-17A	protein	We reasoned that since the IL-17A protein is almost exclusively present in a dimeric form, dimerizing the IL-17A binding peptides could result in an improvement in binding affinity and inhibitory activity.	RESULTS
77	84	dimeric	oligomeric_state	We reasoned that since the IL-17A protein is almost exclusively present in a dimeric form, dimerizing the IL-17A binding peptides could result in an improvement in binding affinity and inhibitory activity.	RESULTS
91	101	dimerizing	oligomeric_state	We reasoned that since the IL-17A protein is almost exclusively present in a dimeric form, dimerizing the IL-17A binding peptides could result in an improvement in binding affinity and inhibitory activity.	RESULTS
106	112	IL-17A	protein	We reasoned that since the IL-17A protein is almost exclusively present in a dimeric form, dimerizing the IL-17A binding peptides could result in an improvement in binding affinity and inhibitory activity.	RESULTS
164	180	binding affinity	evidence	We reasoned that since the IL-17A protein is almost exclusively present in a dimeric form, dimerizing the IL-17A binding peptides could result in an improvement in binding affinity and inhibitory activity.	RESULTS
0	10	Homodimers	oligomeric_state	Homodimers of HAP were made through attachment of polyethylene glycol (PEG) spacers of different lengths at amino acids 4, 7 and 14, as these positions were identified in the alanine scan analysis as not contributing significantly to the activity, and at each N-terminus (Supplementary Table S2).	RESULTS
14	17	HAP	chemical	Homodimers of HAP were made through attachment of polyethylene glycol (PEG) spacers of different lengths at amino acids 4, 7 and 14, as these positions were identified in the alanine scan analysis as not contributing significantly to the activity, and at each N-terminus (Supplementary Table S2).	RESULTS
50	69	polyethylene glycol	chemical	Homodimers of HAP were made through attachment of polyethylene glycol (PEG) spacers of different lengths at amino acids 4, 7 and 14, as these positions were identified in the alanine scan analysis as not contributing significantly to the activity, and at each N-terminus (Supplementary Table S2).	RESULTS
71	74	PEG	chemical	Homodimers of HAP were made through attachment of polyethylene glycol (PEG) spacers of different lengths at amino acids 4, 7 and 14, as these positions were identified in the alanine scan analysis as not contributing significantly to the activity, and at each N-terminus (Supplementary Table S2).	RESULTS
120	121	4	residue_number	Homodimers of HAP were made through attachment of polyethylene glycol (PEG) spacers of different lengths at amino acids 4, 7 and 14, as these positions were identified in the alanine scan analysis as not contributing significantly to the activity, and at each N-terminus (Supplementary Table S2).	RESULTS
123	124	7	residue_number	Homodimers of HAP were made through attachment of polyethylene glycol (PEG) spacers of different lengths at amino acids 4, 7 and 14, as these positions were identified in the alanine scan analysis as not contributing significantly to the activity, and at each N-terminus (Supplementary Table S2).	RESULTS
129	131	14	residue_number	Homodimers of HAP were made through attachment of polyethylene glycol (PEG) spacers of different lengths at amino acids 4, 7 and 14, as these positions were identified in the alanine scan analysis as not contributing significantly to the activity, and at each N-terminus (Supplementary Table S2).	RESULTS
175	196	alanine scan analysis	experimental_method	Homodimers of HAP were made through attachment of polyethylene glycol (PEG) spacers of different lengths at amino acids 4, 7 and 14, as these positions were identified in the alanine scan analysis as not contributing significantly to the activity, and at each N-terminus (Supplementary Table S2).	RESULTS
34	50	pentafluoroester	chemical	Due to the high reactivity of the pentafluoroester (PFP) group used as the activating group in the PEG, the histidine at position 2 and the lysine at position 15 were replaced with threonine and dimethyllysine respectively to prevent formation of side products, which resulted in peptide 38 that was comparable in activity with HAP.	RESULTS
52	55	PFP	chemical	Due to the high reactivity of the pentafluoroester (PFP) group used as the activating group in the PEG, the histidine at position 2 and the lysine at position 15 were replaced with threonine and dimethyllysine respectively to prevent formation of side products, which resulted in peptide 38 that was comparable in activity with HAP.	RESULTS
99	102	PEG	chemical	Due to the high reactivity of the pentafluoroester (PFP) group used as the activating group in the PEG, the histidine at position 2 and the lysine at position 15 were replaced with threonine and dimethyllysine respectively to prevent formation of side products, which resulted in peptide 38 that was comparable in activity with HAP.	RESULTS
108	117	histidine	residue_name	Due to the high reactivity of the pentafluoroester (PFP) group used as the activating group in the PEG, the histidine at position 2 and the lysine at position 15 were replaced with threonine and dimethyllysine respectively to prevent formation of side products, which resulted in peptide 38 that was comparable in activity with HAP.	RESULTS
130	131	2	residue_number	Due to the high reactivity of the pentafluoroester (PFP) group used as the activating group in the PEG, the histidine at position 2 and the lysine at position 15 were replaced with threonine and dimethyllysine respectively to prevent formation of side products, which resulted in peptide 38 that was comparable in activity with HAP.	RESULTS
140	146	lysine	residue_name	Due to the high reactivity of the pentafluoroester (PFP) group used as the activating group in the PEG, the histidine at position 2 and the lysine at position 15 were replaced with threonine and dimethyllysine respectively to prevent formation of side products, which resulted in peptide 38 that was comparable in activity with HAP.	RESULTS
159	161	15	residue_number	Due to the high reactivity of the pentafluoroester (PFP) group used as the activating group in the PEG, the histidine at position 2 and the lysine at position 15 were replaced with threonine and dimethyllysine respectively to prevent formation of side products, which resulted in peptide 38 that was comparable in activity with HAP.	RESULTS
181	190	threonine	residue_name	Due to the high reactivity of the pentafluoroester (PFP) group used as the activating group in the PEG, the histidine at position 2 and the lysine at position 15 were replaced with threonine and dimethyllysine respectively to prevent formation of side products, which resulted in peptide 38 that was comparable in activity with HAP.	RESULTS
195	209	dimethyllysine	residue_name	Due to the high reactivity of the pentafluoroester (PFP) group used as the activating group in the PEG, the histidine at position 2 and the lysine at position 15 were replaced with threonine and dimethyllysine respectively to prevent formation of side products, which resulted in peptide 38 that was comparable in activity with HAP.	RESULTS
280	290	peptide 38	chemical	Due to the high reactivity of the pentafluoroester (PFP) group used as the activating group in the PEG, the histidine at position 2 and the lysine at position 15 were replaced with threonine and dimethyllysine respectively to prevent formation of side products, which resulted in peptide 38 that was comparable in activity with HAP.	RESULTS
328	331	HAP	chemical	Due to the high reactivity of the pentafluoroester (PFP) group used as the activating group in the PEG, the histidine at position 2 and the lysine at position 15 were replaced with threonine and dimethyllysine respectively to prevent formation of side products, which resulted in peptide 38 that was comparable in activity with HAP.	RESULTS
36	43	dimeric	oligomeric_state	This exercise revealed that several dimeric peptides with the longer PEG21 spacer were significantly more potent than the monomer peptide in the cell-based assay (Supplementary Table S2).	RESULTS
44	52	peptides	chemical	This exercise revealed that several dimeric peptides with the longer PEG21 spacer were significantly more potent than the monomer peptide in the cell-based assay (Supplementary Table S2).	RESULTS
69	74	PEG21	chemical	This exercise revealed that several dimeric peptides with the longer PEG21 spacer were significantly more potent than the monomer peptide in the cell-based assay (Supplementary Table S2).	RESULTS
122	129	monomer	oligomeric_state	This exercise revealed that several dimeric peptides with the longer PEG21 spacer were significantly more potent than the monomer peptide in the cell-based assay (Supplementary Table S2).	RESULTS
145	161	cell-based assay	experimental_method	This exercise revealed that several dimeric peptides with the longer PEG21 spacer were significantly more potent than the monomer peptide in the cell-based assay (Supplementary Table S2).	RESULTS
0	10	Peptide 45	chemical	Peptide 45, dimerized via attachment of a PEG21 spacer at position 14 (Supplementary Scheme S1 and Figure S3), was the most potent with cellular IC50 of 0.1 nM. This significant improvement in antagonism was not seen in the peptide monomer functionalized with a PEG21 group at position 14 as peptide 48 had an IC50 of 21 nM (Supplementary Scheme S2).	RESULTS
12	21	dimerized	oligomeric_state	Peptide 45, dimerized via attachment of a PEG21 spacer at position 14 (Supplementary Scheme S1 and Figure S3), was the most potent with cellular IC50 of 0.1 nM. This significant improvement in antagonism was not seen in the peptide monomer functionalized with a PEG21 group at position 14 as peptide 48 had an IC50 of 21 nM (Supplementary Scheme S2).	RESULTS
42	47	PEG21	chemical	Peptide 45, dimerized via attachment of a PEG21 spacer at position 14 (Supplementary Scheme S1 and Figure S3), was the most potent with cellular IC50 of 0.1 nM. This significant improvement in antagonism was not seen in the peptide monomer functionalized with a PEG21 group at position 14 as peptide 48 had an IC50 of 21 nM (Supplementary Scheme S2).	RESULTS
67	69	14	residue_number	Peptide 45, dimerized via attachment of a PEG21 spacer at position 14 (Supplementary Scheme S1 and Figure S3), was the most potent with cellular IC50 of 0.1 nM. This significant improvement in antagonism was not seen in the peptide monomer functionalized with a PEG21 group at position 14 as peptide 48 had an IC50 of 21 nM (Supplementary Scheme S2).	RESULTS
145	149	IC50	evidence	Peptide 45, dimerized via attachment of a PEG21 spacer at position 14 (Supplementary Scheme S1 and Figure S3), was the most potent with cellular IC50 of 0.1 nM. This significant improvement in antagonism was not seen in the peptide monomer functionalized with a PEG21 group at position 14 as peptide 48 had an IC50 of 21 nM (Supplementary Scheme S2).	RESULTS
232	239	monomer	oligomeric_state	Peptide 45, dimerized via attachment of a PEG21 spacer at position 14 (Supplementary Scheme S1 and Figure S3), was the most potent with cellular IC50 of 0.1 nM. This significant improvement in antagonism was not seen in the peptide monomer functionalized with a PEG21 group at position 14 as peptide 48 had an IC50 of 21 nM (Supplementary Scheme S2).	RESULTS
262	267	PEG21	chemical	Peptide 45, dimerized via attachment of a PEG21 spacer at position 14 (Supplementary Scheme S1 and Figure S3), was the most potent with cellular IC50 of 0.1 nM. This significant improvement in antagonism was not seen in the peptide monomer functionalized with a PEG21 group at position 14 as peptide 48 had an IC50 of 21 nM (Supplementary Scheme S2).	RESULTS
286	288	14	residue_number	Peptide 45, dimerized via attachment of a PEG21 spacer at position 14 (Supplementary Scheme S1 and Figure S3), was the most potent with cellular IC50 of 0.1 nM. This significant improvement in antagonism was not seen in the peptide monomer functionalized with a PEG21 group at position 14 as peptide 48 had an IC50 of 21 nM (Supplementary Scheme S2).	RESULTS
292	302	peptide 48	chemical	Peptide 45, dimerized via attachment of a PEG21 spacer at position 14 (Supplementary Scheme S1 and Figure S3), was the most potent with cellular IC50 of 0.1 nM. This significant improvement in antagonism was not seen in the peptide monomer functionalized with a PEG21 group at position 14 as peptide 48 had an IC50 of 21 nM (Supplementary Scheme S2).	RESULTS
310	314	IC50	evidence	Peptide 45, dimerized via attachment of a PEG21 spacer at position 14 (Supplementary Scheme S1 and Figure S3), was the most potent with cellular IC50 of 0.1 nM. This significant improvement in antagonism was not seen in the peptide monomer functionalized with a PEG21 group at position 14 as peptide 48 had an IC50 of 21 nM (Supplementary Scheme S2).	RESULTS
36	43	dimeric	oligomeric_state	The species cross-reactivity of the dimeric peptide 45 and HAP were assessed in a murine functional cell assay using 15 ng/ml murine IL-17A.	RESULTS
44	54	peptide 45	chemical	The species cross-reactivity of the dimeric peptide 45 and HAP were assessed in a murine functional cell assay using 15 ng/ml murine IL-17A.	RESULTS
59	62	HAP	chemical	The species cross-reactivity of the dimeric peptide 45 and HAP were assessed in a murine functional cell assay using 15 ng/ml murine IL-17A.	RESULTS
82	110	murine functional cell assay	experimental_method	The species cross-reactivity of the dimeric peptide 45 and HAP were assessed in a murine functional cell assay using 15 ng/ml murine IL-17A.	RESULTS
126	132	murine	taxonomy_domain	The species cross-reactivity of the dimeric peptide 45 and HAP were assessed in a murine functional cell assay using 15 ng/ml murine IL-17A.	RESULTS
133	139	IL-17A	protein	The species cross-reactivity of the dimeric peptide 45 and HAP were assessed in a murine functional cell assay using 15 ng/ml murine IL-17A.	RESULTS
0	10	Peptide 45	chemical	Peptide 45 blocked the receptor binding of murine IL-17A although with potency two orders of magnitude weaker than that observed against human IL-17A (IC50 = 41 nM vs IC50 = 0.1 nM, respectively).	RESULTS
23	31	receptor	protein_type	Peptide 45 blocked the receptor binding of murine IL-17A although with potency two orders of magnitude weaker than that observed against human IL-17A (IC50 = 41 nM vs IC50 = 0.1 nM, respectively).	RESULTS
43	49	murine	taxonomy_domain	Peptide 45 blocked the receptor binding of murine IL-17A although with potency two orders of magnitude weaker than that observed against human IL-17A (IC50 = 41 nM vs IC50 = 0.1 nM, respectively).	RESULTS
50	56	IL-17A	protein	Peptide 45 blocked the receptor binding of murine IL-17A although with potency two orders of magnitude weaker than that observed against human IL-17A (IC50 = 41 nM vs IC50 = 0.1 nM, respectively).	RESULTS
137	142	human	species	Peptide 45 blocked the receptor binding of murine IL-17A although with potency two orders of magnitude weaker than that observed against human IL-17A (IC50 = 41 nM vs IC50 = 0.1 nM, respectively).	RESULTS
143	149	IL-17A	protein	Peptide 45 blocked the receptor binding of murine IL-17A although with potency two orders of magnitude weaker than that observed against human IL-17A (IC50 = 41 nM vs IC50 = 0.1 nM, respectively).	RESULTS
151	155	IC50	evidence	Peptide 45 blocked the receptor binding of murine IL-17A although with potency two orders of magnitude weaker than that observed against human IL-17A (IC50 = 41 nM vs IC50 = 0.1 nM, respectively).	RESULTS
167	171	IC50	evidence	Peptide 45 blocked the receptor binding of murine IL-17A although with potency two orders of magnitude weaker than that observed against human IL-17A (IC50 = 41 nM vs IC50 = 0.1 nM, respectively).	RESULTS
4	11	monomer	oligomeric_state	The monomer HAP was much weaker (IC50 >1 μM) in inhibiting murine IL-17A signaling (Supplementary Figure S4).	RESULTS
12	15	HAP	chemical	The monomer HAP was much weaker (IC50 >1 μM) in inhibiting murine IL-17A signaling (Supplementary Figure S4).	RESULTS
33	37	IC50	evidence	The monomer HAP was much weaker (IC50 >1 μM) in inhibiting murine IL-17A signaling (Supplementary Figure S4).	RESULTS
59	65	murine	taxonomy_domain	The monomer HAP was much weaker (IC50 >1 μM) in inhibiting murine IL-17A signaling (Supplementary Figure S4).	RESULTS
66	72	IL-17A	protein	The monomer HAP was much weaker (IC50 >1 μM) in inhibiting murine IL-17A signaling (Supplementary Figure S4).	RESULTS
13	20	dimeric	oligomeric_state	Although the dimeric peptide 45 is much more potent than HAP in the cell-based assay, in subsequent studies we decided to focus our efforts solely on characterizations of the monomeric peptide HAP in hopes to identify smaller peptide inhibitors containing the best minimal functional group.	RESULTS
21	31	peptide 45	chemical	Although the dimeric peptide 45 is much more potent than HAP in the cell-based assay, in subsequent studies we decided to focus our efforts solely on characterizations of the monomeric peptide HAP in hopes to identify smaller peptide inhibitors containing the best minimal functional group.	RESULTS
57	60	HAP	chemical	Although the dimeric peptide 45 is much more potent than HAP in the cell-based assay, in subsequent studies we decided to focus our efforts solely on characterizations of the monomeric peptide HAP in hopes to identify smaller peptide inhibitors containing the best minimal functional group.	RESULTS
68	84	cell-based assay	experimental_method	Although the dimeric peptide 45 is much more potent than HAP in the cell-based assay, in subsequent studies we decided to focus our efforts solely on characterizations of the monomeric peptide HAP in hopes to identify smaller peptide inhibitors containing the best minimal functional group.	RESULTS
175	184	monomeric	oligomeric_state	Although the dimeric peptide 45 is much more potent than HAP in the cell-based assay, in subsequent studies we decided to focus our efforts solely on characterizations of the monomeric peptide HAP in hopes to identify smaller peptide inhibitors containing the best minimal functional group.	RESULTS
193	196	HAP	chemical	Although the dimeric peptide 45 is much more potent than HAP in the cell-based assay, in subsequent studies we decided to focus our efforts solely on characterizations of the monomeric peptide HAP in hopes to identify smaller peptide inhibitors containing the best minimal functional group.	RESULTS
29	32	HAP	chemical	Orthogonal assays to confirm HAP antagonism	RESULTS
43	46	HAP	chemical	To further characterize the interaction of HAP with IL-17A, we set out to determine its in vitro binding affinity, specificity and kinetic profile using Surface Plasmon Resonance (SPR) methods (Fig. 1A).	RESULTS
52	58	IL-17A	protein	To further characterize the interaction of HAP with IL-17A, we set out to determine its in vitro binding affinity, specificity and kinetic profile using Surface Plasmon Resonance (SPR) methods (Fig. 1A).	RESULTS
97	113	binding affinity	evidence	To further characterize the interaction of HAP with IL-17A, we set out to determine its in vitro binding affinity, specificity and kinetic profile using Surface Plasmon Resonance (SPR) methods (Fig. 1A).	RESULTS
131	146	kinetic profile	evidence	To further characterize the interaction of HAP with IL-17A, we set out to determine its in vitro binding affinity, specificity and kinetic profile using Surface Plasmon Resonance (SPR) methods (Fig. 1A).	RESULTS
153	178	Surface Plasmon Resonance	experimental_method	To further characterize the interaction of HAP with IL-17A, we set out to determine its in vitro binding affinity, specificity and kinetic profile using Surface Plasmon Resonance (SPR) methods (Fig. 1A).	RESULTS
180	183	SPR	experimental_method	To further characterize the interaction of HAP with IL-17A, we set out to determine its in vitro binding affinity, specificity and kinetic profile using Surface Plasmon Resonance (SPR) methods (Fig. 1A).	RESULTS
0	3	HAP	chemical	HAP binds to immobilized human IL-17A homodimer tightly (Table 3).	RESULTS
25	30	human	species	HAP binds to immobilized human IL-17A homodimer tightly (Table 3).	RESULTS
31	37	IL-17A	protein	HAP binds to immobilized human IL-17A homodimer tightly (Table 3).	RESULTS
38	47	homodimer	oligomeric_state	HAP binds to immobilized human IL-17A homodimer tightly (Table 3).	RESULTS
23	31	affinity	evidence	It has slightly weaker affinity for human IL-17A/F heterodimer and >10 fold weaker affinity for mouse IL-17A (Table 3).	RESULTS
36	41	human	species	It has slightly weaker affinity for human IL-17A/F heterodimer and >10 fold weaker affinity for mouse IL-17A (Table 3).	RESULTS
42	50	IL-17A/F	complex_assembly	It has slightly weaker affinity for human IL-17A/F heterodimer and >10 fold weaker affinity for mouse IL-17A (Table 3).	RESULTS
51	62	heterodimer	oligomeric_state	It has slightly weaker affinity for human IL-17A/F heterodimer and >10 fold weaker affinity for mouse IL-17A (Table 3).	RESULTS
83	91	affinity	evidence	It has slightly weaker affinity for human IL-17A/F heterodimer and >10 fold weaker affinity for mouse IL-17A (Table 3).	RESULTS
96	101	mouse	taxonomy_domain	It has slightly weaker affinity for human IL-17A/F heterodimer and >10 fold weaker affinity for mouse IL-17A (Table 3).	RESULTS
102	108	IL-17A	protein	It has slightly weaker affinity for human IL-17A/F heterodimer and >10 fold weaker affinity for mouse IL-17A (Table 3).	RESULTS
0	3	HAP	chemical	HAP does not show significant binding to immobilized human IL-17F homodimer or IL-17RA at concentrations up to 100 nM.	RESULTS
53	58	human	species	HAP does not show significant binding to immobilized human IL-17F homodimer or IL-17RA at concentrations up to 100 nM.	RESULTS
59	65	IL-17F	protein	HAP does not show significant binding to immobilized human IL-17F homodimer or IL-17RA at concentrations up to 100 nM.	RESULTS
66	75	homodimer	oligomeric_state	HAP does not show significant binding to immobilized human IL-17F homodimer or IL-17RA at concentrations up to 100 nM.	RESULTS
79	86	IL-17RA	protein	HAP does not show significant binding to immobilized human IL-17F homodimer or IL-17RA at concentrations up to 100 nM.	RESULTS
52	57	human	species	Additionally, we investigated the antagonism of the human IL-17A/IL-17RA interaction by HAP using orthogonal methods including SPR and Förster resonance energy transfer (FRET) competition assays (Fig. 1B,C).	RESULTS
58	72	IL-17A/IL-17RA	complex_assembly	Additionally, we investigated the antagonism of the human IL-17A/IL-17RA interaction by HAP using orthogonal methods including SPR and Förster resonance energy transfer (FRET) competition assays (Fig. 1B,C).	RESULTS
88	91	HAP	chemical	Additionally, we investigated the antagonism of the human IL-17A/IL-17RA interaction by HAP using orthogonal methods including SPR and Förster resonance energy transfer (FRET) competition assays (Fig. 1B,C).	RESULTS
127	130	SPR	experimental_method	Additionally, we investigated the antagonism of the human IL-17A/IL-17RA interaction by HAP using orthogonal methods including SPR and Förster resonance energy transfer (FRET) competition assays (Fig. 1B,C).	RESULTS
135	194	Förster resonance energy transfer (FRET) competition assays	experimental_method	Additionally, we investigated the antagonism of the human IL-17A/IL-17RA interaction by HAP using orthogonal methods including SPR and Förster resonance energy transfer (FRET) competition assays (Fig. 1B,C).	RESULTS
30	36	IL-17A	protein	In both assays, incubation of IL-17A with HAP effectively blocks the binding of IL-17A to immobilized IL-17RA with similar sub-nM IC50 (Table 3).	RESULTS
42	45	HAP	chemical	In both assays, incubation of IL-17A with HAP effectively blocks the binding of IL-17A to immobilized IL-17RA with similar sub-nM IC50 (Table 3).	RESULTS
80	86	IL-17A	protein	In both assays, incubation of IL-17A with HAP effectively blocks the binding of IL-17A to immobilized IL-17RA with similar sub-nM IC50 (Table 3).	RESULTS
90	101	immobilized	protein_state	In both assays, incubation of IL-17A with HAP effectively blocks the binding of IL-17A to immobilized IL-17RA with similar sub-nM IC50 (Table 3).	RESULTS
102	109	IL-17RA	protein	In both assays, incubation of IL-17A with HAP effectively blocks the binding of IL-17A to immobilized IL-17RA with similar sub-nM IC50 (Table 3).	RESULTS
130	134	IC50	evidence	In both assays, incubation of IL-17A with HAP effectively blocks the binding of IL-17A to immobilized IL-17RA with similar sub-nM IC50 (Table 3).	RESULTS
0	3	HAP	chemical	HAP blocks IL-17A signaling in a human primary cell assay	RESULTS
11	17	IL-17A	protein	HAP blocks IL-17A signaling in a human primary cell assay	RESULTS
33	38	human	species	HAP blocks IL-17A signaling in a human primary cell assay	RESULTS
13	19	IL-17A	protein	While either IL-17A or TNF-α alone can stimulate the release of multiple inflammatory cytokines, when acting together they can synergistically enhance each other’s effects (Supplementary Figure S5).	RESULTS
23	28	TNF-α	protein	While either IL-17A or TNF-α alone can stimulate the release of multiple inflammatory cytokines, when acting together they can synergistically enhance each other’s effects (Supplementary Figure S5).	RESULTS
86	95	cytokines	protein_type	While either IL-17A or TNF-α alone can stimulate the release of multiple inflammatory cytokines, when acting together they can synergistically enhance each other’s effects (Supplementary Figure S5).	RESULTS
31	37	IL-17A	protein	These integrative responses to IL-17A and TNF-α in human keratinocytes have been reported to account for key inflammatory pathogenic circuits in psoriasis.	RESULTS
42	47	TNF-α	protein	These integrative responses to IL-17A and TNF-α in human keratinocytes have been reported to account for key inflammatory pathogenic circuits in psoriasis.	RESULTS
51	56	human	species	These integrative responses to IL-17A and TNF-α in human keratinocytes have been reported to account for key inflammatory pathogenic circuits in psoriasis.	RESULTS
24	27	HAP	chemical	Thus, we chose to study HAP’s efficacy in blocking the production of IL-8, IL-6 and CCL-20 by primary human keratinocytes stimulated by IL-17A in the presence of TNF-α, an assay which may be more disease-relevant.	RESULTS
69	73	IL-8	protein_type	Thus, we chose to study HAP’s efficacy in blocking the production of IL-8, IL-6 and CCL-20 by primary human keratinocytes stimulated by IL-17A in the presence of TNF-α, an assay which may be more disease-relevant.	RESULTS
75	79	IL-6	protein_type	Thus, we chose to study HAP’s efficacy in blocking the production of IL-8, IL-6 and CCL-20 by primary human keratinocytes stimulated by IL-17A in the presence of TNF-α, an assay which may be more disease-relevant.	RESULTS
84	90	CCL-20	protein_type	Thus, we chose to study HAP’s efficacy in blocking the production of IL-8, IL-6 and CCL-20 by primary human keratinocytes stimulated by IL-17A in the presence of TNF-α, an assay which may be more disease-relevant.	RESULTS
102	107	human	species	Thus, we chose to study HAP’s efficacy in blocking the production of IL-8, IL-6 and CCL-20 by primary human keratinocytes stimulated by IL-17A in the presence of TNF-α, an assay which may be more disease-relevant.	RESULTS
136	142	IL-17A	protein	Thus, we chose to study HAP’s efficacy in blocking the production of IL-8, IL-6 and CCL-20 by primary human keratinocytes stimulated by IL-17A in the presence of TNF-α, an assay which may be more disease-relevant.	RESULTS
162	167	TNF-α	protein	Thus, we chose to study HAP’s efficacy in blocking the production of IL-8, IL-6 and CCL-20 by primary human keratinocytes stimulated by IL-17A in the presence of TNF-α, an assay which may be more disease-relevant.	RESULTS
0	3	HAP	chemical	HAP inhibits the production of all three cytokines in a dose-dependent fashion (Fig. 1D).	RESULTS
41	50	cytokines	protein_type	HAP inhibits the production of all three cytokines in a dose-dependent fashion (Fig. 1D).	RESULTS
38	42	IL-8	protein_type	Significantly, the baseline levels of IL-8, IL-6 and CCL-20 stimulated by TNF-α alone are not inhibited by HAP, further indicating the selectivity of HAP (Fig. 1D).	RESULTS
44	48	IL-6	protein_type	Significantly, the baseline levels of IL-8, IL-6 and CCL-20 stimulated by TNF-α alone are not inhibited by HAP, further indicating the selectivity of HAP (Fig. 1D).	RESULTS
53	59	CCL-20	protein_type	Significantly, the baseline levels of IL-8, IL-6 and CCL-20 stimulated by TNF-α alone are not inhibited by HAP, further indicating the selectivity of HAP (Fig. 1D).	RESULTS
74	79	TNF-α	protein	Significantly, the baseline levels of IL-8, IL-6 and CCL-20 stimulated by TNF-α alone are not inhibited by HAP, further indicating the selectivity of HAP (Fig. 1D).	RESULTS
107	110	HAP	chemical	Significantly, the baseline levels of IL-8, IL-6 and CCL-20 stimulated by TNF-α alone are not inhibited by HAP, further indicating the selectivity of HAP (Fig. 1D).	RESULTS
150	153	HAP	chemical	Significantly, the baseline levels of IL-8, IL-6 and CCL-20 stimulated by TNF-α alone are not inhibited by HAP, further indicating the selectivity of HAP (Fig. 1D).	RESULTS
172	177	TNF-α	protein	Such pharmacological selectivity may be important to suppress inflammatory pathogenic circuits in psoriasis, while sparing the anti-infectious immune responses produced by TNF-α.	RESULTS
20	24	IC50	evidence	The relatively high IC50 values in this assay (Table 3) are probably due to the high IL-17A concentration (100 ng/ml) needed for detection of IL-6.	RESULTS
85	91	IL-17A	protein	The relatively high IC50 values in this assay (Table 3) are probably due to the high IL-17A concentration (100 ng/ml) needed for detection of IL-6.	RESULTS
142	146	IL-6	protein_type	The relatively high IC50 values in this assay (Table 3) are probably due to the high IL-17A concentration (100 ng/ml) needed for detection of IL-6.	RESULTS
34	40	IL-17A	protein	As a reference, a commercial anti-IL-17A antibody (R&D Systems) inhibits the production of IL-8 with an IC50 of 13(±6) nM (N = 3).	RESULTS
41	49	antibody	protein_type	As a reference, a commercial anti-IL-17A antibody (R&D Systems) inhibits the production of IL-8 with an IC50 of 13(±6) nM (N = 3).	RESULTS
91	95	IL-8	protein_type	As a reference, a commercial anti-IL-17A antibody (R&D Systems) inhibits the production of IL-8 with an IC50 of 13(±6) nM (N = 3).	RESULTS
104	108	IC50	evidence	As a reference, a commercial anti-IL-17A antibody (R&D Systems) inhibits the production of IL-8 with an IC50 of 13(±6) nM (N = 3).	RESULTS
12	16	IC50	evidence	Indeed, the IC50 was 14(±9) nM (N = 12) for HAP inhibition of IL-8 production when only 5 ng/ml IL-17A was used in this assay.	RESULTS
44	47	HAP	chemical	Indeed, the IC50 was 14(±9) nM (N = 12) for HAP inhibition of IL-8 production when only 5 ng/ml IL-17A was used in this assay.	RESULTS
62	66	IL-8	protein_type	Indeed, the IC50 was 14(±9) nM (N = 12) for HAP inhibition of IL-8 production when only 5 ng/ml IL-17A was used in this assay.	RESULTS
96	102	IL-17A	protein	Indeed, the IC50 was 14(±9) nM (N = 12) for HAP inhibition of IL-8 production when only 5 ng/ml IL-17A was used in this assay.	RESULTS
34	40	IL-17A	protein	In patients, the concentration of IL-17A in psoriatic lesions is reported to be 0.01 ng/ml, well below the EC50 (5–10ng/ml) of IL-17A induced IL-8 production in vitro.	RESULTS
127	133	IL-17A	protein	In patients, the concentration of IL-17A in psoriatic lesions is reported to be 0.01 ng/ml, well below the EC50 (5–10ng/ml) of IL-17A induced IL-8 production in vitro.	RESULTS
142	146	IL-8	protein_type	In patients, the concentration of IL-17A in psoriatic lesions is reported to be 0.01 ng/ml, well below the EC50 (5–10ng/ml) of IL-17A induced IL-8 production in vitro.	RESULTS
11	30	keratinocytes assay	experimental_method	Similar to keratinocytes assay results, while HAP inhibits IL-17A stimulated IL-6 production by BJ human fibroblast potently (IC50 of 17 nM), it does not inhibit TNF-α stimulated IL-6 production at concentrations up to 10 μM (Supplementary Figure S2).	RESULTS
46	49	HAP	chemical	Similar to keratinocytes assay results, while HAP inhibits IL-17A stimulated IL-6 production by BJ human fibroblast potently (IC50 of 17 nM), it does not inhibit TNF-α stimulated IL-6 production at concentrations up to 10 μM (Supplementary Figure S2).	RESULTS
59	65	IL-17A	protein	Similar to keratinocytes assay results, while HAP inhibits IL-17A stimulated IL-6 production by BJ human fibroblast potently (IC50 of 17 nM), it does not inhibit TNF-α stimulated IL-6 production at concentrations up to 10 μM (Supplementary Figure S2).	RESULTS
77	81	IL-6	protein_type	Similar to keratinocytes assay results, while HAP inhibits IL-17A stimulated IL-6 production by BJ human fibroblast potently (IC50 of 17 nM), it does not inhibit TNF-α stimulated IL-6 production at concentrations up to 10 μM (Supplementary Figure S2).	RESULTS
99	104	human	species	Similar to keratinocytes assay results, while HAP inhibits IL-17A stimulated IL-6 production by BJ human fibroblast potently (IC50 of 17 nM), it does not inhibit TNF-α stimulated IL-6 production at concentrations up to 10 μM (Supplementary Figure S2).	RESULTS
126	130	IC50	evidence	Similar to keratinocytes assay results, while HAP inhibits IL-17A stimulated IL-6 production by BJ human fibroblast potently (IC50 of 17 nM), it does not inhibit TNF-α stimulated IL-6 production at concentrations up to 10 μM (Supplementary Figure S2).	RESULTS
162	167	TNF-α	protein	Similar to keratinocytes assay results, while HAP inhibits IL-17A stimulated IL-6 production by BJ human fibroblast potently (IC50 of 17 nM), it does not inhibit TNF-α stimulated IL-6 production at concentrations up to 10 μM (Supplementary Figure S2).	RESULTS
179	183	IL-6	protein_type	Similar to keratinocytes assay results, while HAP inhibits IL-17A stimulated IL-6 production by BJ human fibroblast potently (IC50 of 17 nM), it does not inhibit TNF-α stimulated IL-6 production at concentrations up to 10 μM (Supplementary Figure S2).	RESULTS
0	43	Crystallization and structure determination	experimental_method	Crystallization and structure determination	RESULTS
10	32	crystallization trials	experimental_method	Extensive crystallization trials, either by co-crystallization or by soaking HAP into preformed apo IL-17A crystals, failed to lead to an IL-17A/HAP complex crystals.	RESULTS
44	62	co-crystallization	experimental_method	Extensive crystallization trials, either by co-crystallization or by soaking HAP into preformed apo IL-17A crystals, failed to lead to an IL-17A/HAP complex crystals.	RESULTS
69	76	soaking	experimental_method	Extensive crystallization trials, either by co-crystallization or by soaking HAP into preformed apo IL-17A crystals, failed to lead to an IL-17A/HAP complex crystals.	RESULTS
77	80	HAP	chemical	Extensive crystallization trials, either by co-crystallization or by soaking HAP into preformed apo IL-17A crystals, failed to lead to an IL-17A/HAP complex crystals.	RESULTS
96	99	apo	protein_state	Extensive crystallization trials, either by co-crystallization or by soaking HAP into preformed apo IL-17A crystals, failed to lead to an IL-17A/HAP complex crystals.	RESULTS
100	106	IL-17A	protein	Extensive crystallization trials, either by co-crystallization or by soaking HAP into preformed apo IL-17A crystals, failed to lead to an IL-17A/HAP complex crystals.	RESULTS
107	115	crystals	evidence	Extensive crystallization trials, either by co-crystallization or by soaking HAP into preformed apo IL-17A crystals, failed to lead to an IL-17A/HAP complex crystals.	RESULTS
138	148	IL-17A/HAP	complex_assembly	Extensive crystallization trials, either by co-crystallization or by soaking HAP into preformed apo IL-17A crystals, failed to lead to an IL-17A/HAP complex crystals.	RESULTS
157	165	crystals	evidence	Extensive crystallization trials, either by co-crystallization or by soaking HAP into preformed apo IL-17A crystals, failed to lead to an IL-17A/HAP complex crystals.	RESULTS
18	21	HAP	chemical	We theorized that HAP binding induced large conformational changes in IL-17A that led to the difficulty of getting an IL-17A/HAP binary complex crystal.	RESULTS
70	76	IL-17A	protein	We theorized that HAP binding induced large conformational changes in IL-17A that led to the difficulty of getting an IL-17A/HAP binary complex crystal.	RESULTS
118	128	IL-17A/HAP	complex_assembly	We theorized that HAP binding induced large conformational changes in IL-17A that led to the difficulty of getting an IL-17A/HAP binary complex crystal.	RESULTS
144	151	crystal	evidence	We theorized that HAP binding induced large conformational changes in IL-17A that led to the difficulty of getting an IL-17A/HAP binary complex crystal.	RESULTS
20	28	antibody	protein_type	It is known that an antibody antigen-binding fragment (Fab) can be used as crystallization chaperones in crystallizing difficult targets.	RESULTS
29	53	antigen-binding fragment	structure_element	It is known that an antibody antigen-binding fragment (Fab) can be used as crystallization chaperones in crystallizing difficult targets.	RESULTS
55	58	Fab	structure_element	It is known that an antibody antigen-binding fragment (Fab) can be used as crystallization chaperones in crystallizing difficult targets.	RESULTS
21	24	HAP	chemical	We hypothesized that HAP may target the N-terminal of IL-17A which is known to be more flexible than its C-terminal and conformational changes needed for HAP binding may be more likely there.	RESULTS
54	60	IL-17A	protein	We hypothesized that HAP may target the N-terminal of IL-17A which is known to be more flexible than its C-terminal and conformational changes needed for HAP binding may be more likely there.	RESULTS
154	157	HAP	chemical	We hypothesized that HAP may target the N-terminal of IL-17A which is known to be more flexible than its C-terminal and conformational changes needed for HAP binding may be more likely there.	RESULTS
15	23	antibody	protein_type	We designed an antibody Fab known to target the C-terminal half of IL-17A based on a published IL-17A/Fab complex crystal structure, and produced it in HEK293 cells.	RESULTS
24	27	Fab	structure_element	We designed an antibody Fab known to target the C-terminal half of IL-17A based on a published IL-17A/Fab complex crystal structure, and produced it in HEK293 cells.	RESULTS
48	63	C-terminal half	structure_element	We designed an antibody Fab known to target the C-terminal half of IL-17A based on a published IL-17A/Fab complex crystal structure, and produced it in HEK293 cells.	RESULTS
67	73	IL-17A	protein	We designed an antibody Fab known to target the C-terminal half of IL-17A based on a published IL-17A/Fab complex crystal structure, and produced it in HEK293 cells.	RESULTS
95	105	IL-17A/Fab	complex_assembly	We designed an antibody Fab known to target the C-terminal half of IL-17A based on a published IL-17A/Fab complex crystal structure, and produced it in HEK293 cells.	RESULTS
114	131	crystal structure	evidence	We designed an antibody Fab known to target the C-terminal half of IL-17A based on a published IL-17A/Fab complex crystal structure, and produced it in HEK293 cells.	RESULTS
6	15	SPR assay	experimental_method	In an SPR assay HAP and this Fab were able to co-bind IL-17A without large changes in their binding affinities and kinetics, confirming our hypothesis (Supplementary Figure S6).	RESULTS
16	19	HAP	chemical	In an SPR assay HAP and this Fab were able to co-bind IL-17A without large changes in their binding affinities and kinetics, confirming our hypothesis (Supplementary Figure S6).	RESULTS
29	32	Fab	structure_element	In an SPR assay HAP and this Fab were able to co-bind IL-17A without large changes in their binding affinities and kinetics, confirming our hypothesis (Supplementary Figure S6).	RESULTS
54	60	IL-17A	protein	In an SPR assay HAP and this Fab were able to co-bind IL-17A without large changes in their binding affinities and kinetics, confirming our hypothesis (Supplementary Figure S6).	RESULTS
92	110	binding affinities	evidence	In an SPR assay HAP and this Fab were able to co-bind IL-17A without large changes in their binding affinities and kinetics, confirming our hypothesis (Supplementary Figure S6).	RESULTS
115	123	kinetics	evidence	In an SPR assay HAP and this Fab were able to co-bind IL-17A without large changes in their binding affinities and kinetics, confirming our hypothesis (Supplementary Figure S6).	RESULTS
61	64	HAP	chemical	Furthermore, since it binds to an area far away from that of HAP (see below), this Fab should have minimum effects on HAP binding conformation.	RESULTS
83	86	Fab	structure_element	Furthermore, since it binds to an area far away from that of HAP (see below), this Fab should have minimum effects on HAP binding conformation.	RESULTS
118	121	HAP	chemical	Furthermore, since it binds to an area far away from that of HAP (see below), this Fab should have minimum effects on HAP binding conformation.	RESULTS
0	8	Crystals	evidence	Crystals of Fab/IL-17A/HAP ternary complex were obtained readily in crystallization screens.	RESULTS
12	26	Fab/IL-17A/HAP	complex_assembly	Crystals of Fab/IL-17A/HAP ternary complex were obtained readily in crystallization screens.	RESULTS
68	91	crystallization screens	experimental_method	Crystals of Fab/IL-17A/HAP ternary complex were obtained readily in crystallization screens.	RESULTS
0	15	Crystallization	experimental_method	Crystallization of IL-17A and its binding partners was accomplished using two forms of IL-17A.	RESULTS
19	25	IL-17A	protein	Crystallization of IL-17A and its binding partners was accomplished using two forms of IL-17A.	RESULTS
87	93	IL-17A	protein	Crystallization of IL-17A and its binding partners was accomplished using two forms of IL-17A.	RESULTS
64	70	IL-17A	protein	These were, respectively, a presumably more homogeneous form of IL-17A that lacked the disordered N-terminal peptide and a full-length form of the cytokine with a full complement of disulfide bonds.	RESULTS
76	82	lacked	protein_state	These were, respectively, a presumably more homogeneous form of IL-17A that lacked the disordered N-terminal peptide and a full-length form of the cytokine with a full complement of disulfide bonds.	RESULTS
87	97	disordered	protein_state	These were, respectively, a presumably more homogeneous form of IL-17A that lacked the disordered N-terminal peptide and a full-length form of the cytokine with a full complement of disulfide bonds.	RESULTS
98	116	N-terminal peptide	structure_element	These were, respectively, a presumably more homogeneous form of IL-17A that lacked the disordered N-terminal peptide and a full-length form of the cytokine with a full complement of disulfide bonds.	RESULTS
123	134	full-length	protein_state	These were, respectively, a presumably more homogeneous form of IL-17A that lacked the disordered N-terminal peptide and a full-length form of the cytokine with a full complement of disulfide bonds.	RESULTS
147	155	cytokine	protein_type	These were, respectively, a presumably more homogeneous form of IL-17A that lacked the disordered N-terminal peptide and a full-length form of the cytokine with a full complement of disulfide bonds.	RESULTS
182	197	disulfide bonds	ptm	These were, respectively, a presumably more homogeneous form of IL-17A that lacked the disordered N-terminal peptide and a full-length form of the cytokine with a full complement of disulfide bonds.	RESULTS
0	8	Crystals	evidence	Crystals of the Fab/truncated IL-17A/HAP complex diffracted to 2.2 Å, and the Fab/full length IL-17A/HAP complex diffracted to 3.0 Å (Supplementary Table S3).	RESULTS
16	40	Fab/truncated IL-17A/HAP	complex_assembly	Crystals of the Fab/truncated IL-17A/HAP complex diffracted to 2.2 Å, and the Fab/full length IL-17A/HAP complex diffracted to 3.0 Å (Supplementary Table S3).	RESULTS
78	104	Fab/full length IL-17A/HAP	complex_assembly	Crystals of the Fab/truncated IL-17A/HAP complex diffracted to 2.2 Å, and the Fab/full length IL-17A/HAP complex diffracted to 3.0 Å (Supplementary Table S3).	RESULTS
5	15	structures	evidence	Both structures were solved by molecular replacement.	RESULTS
31	52	molecular replacement	experimental_method	Both structures were solved by molecular replacement.	RESULTS
15	27	crystallized	experimental_method	Both complexes crystallized in the space group of P321, with half the complex (1 Fab/1 IL-17A monomer/1 HAP) in the asymmetric unit.	RESULTS
81	84	Fab	structure_element	Both complexes crystallized in the space group of P321, with half the complex (1 Fab/1 IL-17A monomer/1 HAP) in the asymmetric unit.	RESULTS
87	93	IL-17A	protein	Both complexes crystallized in the space group of P321, with half the complex (1 Fab/1 IL-17A monomer/1 HAP) in the asymmetric unit.	RESULTS
94	101	monomer	oligomeric_state	Both complexes crystallized in the space group of P321, with half the complex (1 Fab/1 IL-17A monomer/1 HAP) in the asymmetric unit.	RESULTS
104	107	HAP	chemical	Both complexes crystallized in the space group of P321, with half the complex (1 Fab/1 IL-17A monomer/1 HAP) in the asymmetric unit.	RESULTS
4	10	intact	protein_state	The intact complex can be generated by applying crystallographic 2-fold symmetry.	RESULTS
0	18	Electron densities	evidence	Electron densities for HAP residues Ile1-Asn14 were readily interpretable with the exception of Lys15, which is disordered.	RESULTS
23	26	HAP	chemical	Electron densities for HAP residues Ile1-Asn14 were readily interpretable with the exception of Lys15, which is disordered.	RESULTS
36	46	Ile1-Asn14	residue_range	Electron densities for HAP residues Ile1-Asn14 were readily interpretable with the exception of Lys15, which is disordered.	RESULTS
96	101	Lys15	residue_name_number	Electron densities for HAP residues Ile1-Asn14 were readily interpretable with the exception of Lys15, which is disordered.	RESULTS
112	122	disordered	protein_state	Electron densities for HAP residues Ile1-Asn14 were readily interpretable with the exception of Lys15, which is disordered.	RESULTS
34	51	complex structure	evidence	When considering the protein, the complex structure containing the full length IL-17A is identical to that of the truncated IL-17A, with the exception of Cys106 (Ser106 in the truncated IL-17A), which is disordered.	RESULTS
67	78	full length	protein_state	When considering the protein, the complex structure containing the full length IL-17A is identical to that of the truncated IL-17A, with the exception of Cys106 (Ser106 in the truncated IL-17A), which is disordered.	RESULTS
79	85	IL-17A	protein	When considering the protein, the complex structure containing the full length IL-17A is identical to that of the truncated IL-17A, with the exception of Cys106 (Ser106 in the truncated IL-17A), which is disordered.	RESULTS
114	123	truncated	protein_state	When considering the protein, the complex structure containing the full length IL-17A is identical to that of the truncated IL-17A, with the exception of Cys106 (Ser106 in the truncated IL-17A), which is disordered.	RESULTS
124	130	IL-17A	protein	When considering the protein, the complex structure containing the full length IL-17A is identical to that of the truncated IL-17A, with the exception of Cys106 (Ser106 in the truncated IL-17A), which is disordered.	RESULTS
154	160	Cys106	residue_name_number	When considering the protein, the complex structure containing the full length IL-17A is identical to that of the truncated IL-17A, with the exception of Cys106 (Ser106 in the truncated IL-17A), which is disordered.	RESULTS
162	168	Ser106	residue_name_number	When considering the protein, the complex structure containing the full length IL-17A is identical to that of the truncated IL-17A, with the exception of Cys106 (Ser106 in the truncated IL-17A), which is disordered.	RESULTS
176	185	truncated	protein_state	When considering the protein, the complex structure containing the full length IL-17A is identical to that of the truncated IL-17A, with the exception of Cys106 (Ser106 in the truncated IL-17A), which is disordered.	RESULTS
186	192	IL-17A	protein	When considering the protein, the complex structure containing the full length IL-17A is identical to that of the truncated IL-17A, with the exception of Cys106 (Ser106 in the truncated IL-17A), which is disordered.	RESULTS
204	214	disordered	protein_state	When considering the protein, the complex structure containing the full length IL-17A is identical to that of the truncated IL-17A, with the exception of Cys106 (Ser106 in the truncated IL-17A), which is disordered.	RESULTS
0	6	Cys106	residue_name_number	Cys106 is covalently linked to Cys10 that resides in the disordered N-terminal peptide in the full length IL-17A.	RESULTS
31	36	Cys10	residue_name_number	Cys106 is covalently linked to Cys10 that resides in the disordered N-terminal peptide in the full length IL-17A.	RESULTS
57	67	disordered	protein_state	Cys106 is covalently linked to Cys10 that resides in the disordered N-terminal peptide in the full length IL-17A.	RESULTS
68	86	N-terminal peptide	structure_element	Cys106 is covalently linked to Cys10 that resides in the disordered N-terminal peptide in the full length IL-17A.	RESULTS
94	105	full length	protein_state	Cys106 is covalently linked to Cys10 that resides in the disordered N-terminal peptide in the full length IL-17A.	RESULTS
106	112	IL-17A	protein	Cys106 is covalently linked to Cys10 that resides in the disordered N-terminal peptide in the full length IL-17A.	RESULTS
8	17	structure	evidence	Overall structure of Fab/IL-17A/HAP complex	RESULTS
21	35	Fab/IL-17A/HAP	complex_assembly	Overall structure of Fab/IL-17A/HAP complex	RESULTS
37	46	structure	evidence	In a similar manner to the published structure of Fab/IL-17A complex, two Fab molecules bind symmetrically to the C-terminal of the cytokine dimer, interacting with epitopes from both monomers (Fig. 2A).	RESULTS
50	60	Fab/IL-17A	complex_assembly	In a similar manner to the published structure of Fab/IL-17A complex, two Fab molecules bind symmetrically to the C-terminal of the cytokine dimer, interacting with epitopes from both monomers (Fig. 2A).	RESULTS
74	77	Fab	structure_element	In a similar manner to the published structure of Fab/IL-17A complex, two Fab molecules bind symmetrically to the C-terminal of the cytokine dimer, interacting with epitopes from both monomers (Fig. 2A).	RESULTS
132	140	cytokine	protein_type	In a similar manner to the published structure of Fab/IL-17A complex, two Fab molecules bind symmetrically to the C-terminal of the cytokine dimer, interacting with epitopes from both monomers (Fig. 2A).	RESULTS
141	146	dimer	oligomeric_state	In a similar manner to the published structure of Fab/IL-17A complex, two Fab molecules bind symmetrically to the C-terminal of the cytokine dimer, interacting with epitopes from both monomers (Fig. 2A).	RESULTS
184	192	monomers	oligomeric_state	In a similar manner to the published structure of Fab/IL-17A complex, two Fab molecules bind symmetrically to the C-terminal of the cytokine dimer, interacting with epitopes from both monomers (Fig. 2A).	RESULTS
14	17	HAP	chemical	Two copies of HAP bind to the N-terminal of the cytokine dimer, also symmetrically, and each HAP molecule also interacts with both IL-17A monomers (Fig. 2).	RESULTS
48	56	cytokine	protein_type	Two copies of HAP bind to the N-terminal of the cytokine dimer, also symmetrically, and each HAP molecule also interacts with both IL-17A monomers (Fig. 2).	RESULTS
57	62	dimer	oligomeric_state	Two copies of HAP bind to the N-terminal of the cytokine dimer, also symmetrically, and each HAP molecule also interacts with both IL-17A monomers (Fig. 2).	RESULTS
93	96	HAP	chemical	Two copies of HAP bind to the N-terminal of the cytokine dimer, also symmetrically, and each HAP molecule also interacts with both IL-17A monomers (Fig. 2).	RESULTS
131	137	IL-17A	protein	Two copies of HAP bind to the N-terminal of the cytokine dimer, also symmetrically, and each HAP molecule also interacts with both IL-17A monomers (Fig. 2).	RESULTS
138	146	monomers	oligomeric_state	Two copies of HAP bind to the N-terminal of the cytokine dimer, also symmetrically, and each HAP molecule also interacts with both IL-17A monomers (Fig. 2).	RESULTS
31	42	Secukinumab	chemical	Based on disclosed epitopes of Secukinumab and Ixekizumab, HAP binds to IL-17A at an area that is also different from those of those two antibodies.	RESULTS
47	57	Ixekizumab	chemical	Based on disclosed epitopes of Secukinumab and Ixekizumab, HAP binds to IL-17A at an area that is also different from those of those two antibodies.	RESULTS
59	62	HAP	chemical	Based on disclosed epitopes of Secukinumab and Ixekizumab, HAP binds to IL-17A at an area that is also different from those of those two antibodies.	RESULTS
72	78	IL-17A	protein	Based on disclosed epitopes of Secukinumab and Ixekizumab, HAP binds to IL-17A at an area that is also different from those of those two antibodies.	RESULTS
137	147	antibodies	protein_type	Based on disclosed epitopes of Secukinumab and Ixekizumab, HAP binds to IL-17A at an area that is also different from those of those two antibodies.	RESULTS
15	25	5 residues	residue_range	The N-terminal 5 residues of HAP, 1IHVTI, form an amphipathic β-strand that inserts between β-strand 4 of one IL-17A monomer and β-strand 0 (the first ordered peptide of IL-17A) of the second monomer.	RESULTS
29	32	HAP	chemical	The N-terminal 5 residues of HAP, 1IHVTI, form an amphipathic β-strand that inserts between β-strand 4 of one IL-17A monomer and β-strand 0 (the first ordered peptide of IL-17A) of the second monomer.	RESULTS
34	40	1IHVTI	chemical	The N-terminal 5 residues of HAP, 1IHVTI, form an amphipathic β-strand that inserts between β-strand 4 of one IL-17A monomer and β-strand 0 (the first ordered peptide of IL-17A) of the second monomer.	RESULTS
50	61	amphipathic	protein_state	The N-terminal 5 residues of HAP, 1IHVTI, form an amphipathic β-strand that inserts between β-strand 4 of one IL-17A monomer and β-strand 0 (the first ordered peptide of IL-17A) of the second monomer.	RESULTS
62	70	β-strand	structure_element	The N-terminal 5 residues of HAP, 1IHVTI, form an amphipathic β-strand that inserts between β-strand 4 of one IL-17A monomer and β-strand 0 (the first ordered peptide of IL-17A) of the second monomer.	RESULTS
92	102	β-strand 4	structure_element	The N-terminal 5 residues of HAP, 1IHVTI, form an amphipathic β-strand that inserts between β-strand 4 of one IL-17A monomer and β-strand 0 (the first ordered peptide of IL-17A) of the second monomer.	RESULTS
110	116	IL-17A	protein	The N-terminal 5 residues of HAP, 1IHVTI, form an amphipathic β-strand that inserts between β-strand 4 of one IL-17A monomer and β-strand 0 (the first ordered peptide of IL-17A) of the second monomer.	RESULTS
117	124	monomer	oligomeric_state	The N-terminal 5 residues of HAP, 1IHVTI, form an amphipathic β-strand that inserts between β-strand 4 of one IL-17A monomer and β-strand 0 (the first ordered peptide of IL-17A) of the second monomer.	RESULTS
129	139	β-strand 0	structure_element	The N-terminal 5 residues of HAP, 1IHVTI, form an amphipathic β-strand that inserts between β-strand 4 of one IL-17A monomer and β-strand 0 (the first ordered peptide of IL-17A) of the second monomer.	RESULTS
170	176	IL-17A	protein	The N-terminal 5 residues of HAP, 1IHVTI, form an amphipathic β-strand that inserts between β-strand 4 of one IL-17A monomer and β-strand 0 (the first ordered peptide of IL-17A) of the second monomer.	RESULTS
192	199	monomer	oligomeric_state	The N-terminal 5 residues of HAP, 1IHVTI, form an amphipathic β-strand that inserts between β-strand 4 of one IL-17A monomer and β-strand 0 (the first ordered peptide of IL-17A) of the second monomer.	RESULTS
5	13	β-strand	structure_element	This β-strand is parallel to both strands 0 and 4 (Fig. 3B).	RESULTS
34	49	strands 0 and 4	structure_element	This β-strand is parallel to both strands 0 and 4 (Fig. 3B).	RESULTS
0	9	Strands 0	structure_element	Strands 0 of two IL-17A monomer are antiparallel, as appeared in other IL-17A structures.	RESULTS
17	23	IL-17A	protein	Strands 0 of two IL-17A monomer are antiparallel, as appeared in other IL-17A structures.	RESULTS
24	31	monomer	oligomeric_state	Strands 0 of two IL-17A monomer are antiparallel, as appeared in other IL-17A structures.	RESULTS
71	77	IL-17A	protein	Strands 0 of two IL-17A monomer are antiparallel, as appeared in other IL-17A structures.	RESULTS
78	88	structures	evidence	Strands 0 of two IL-17A monomer are antiparallel, as appeared in other IL-17A structures.	RESULTS
15	25	8 residues	residue_range	The C-terminal 8 residues of the HAP that are ordered in the structure, 7ADLWDWIN, form an amphipathic α-helix interacting with the second IL-17A monomer.	RESULTS
33	36	HAP	chemical	The C-terminal 8 residues of the HAP that are ordered in the structure, 7ADLWDWIN, form an amphipathic α-helix interacting with the second IL-17A monomer.	RESULTS
61	70	structure	evidence	The C-terminal 8 residues of the HAP that are ordered in the structure, 7ADLWDWIN, form an amphipathic α-helix interacting with the second IL-17A monomer.	RESULTS
72	81	7ADLWDWIN	chemical	The C-terminal 8 residues of the HAP that are ordered in the structure, 7ADLWDWIN, form an amphipathic α-helix interacting with the second IL-17A monomer.	RESULTS
91	102	amphipathic	protein_state	The C-terminal 8 residues of the HAP that are ordered in the structure, 7ADLWDWIN, form an amphipathic α-helix interacting with the second IL-17A monomer.	RESULTS
103	110	α-helix	structure_element	The C-terminal 8 residues of the HAP that are ordered in the structure, 7ADLWDWIN, form an amphipathic α-helix interacting with the second IL-17A monomer.	RESULTS
139	145	IL-17A	protein	The C-terminal 8 residues of the HAP that are ordered in the structure, 7ADLWDWIN, form an amphipathic α-helix interacting with the second IL-17A monomer.	RESULTS
146	153	monomer	oligomeric_state	The C-terminal 8 residues of the HAP that are ordered in the structure, 7ADLWDWIN, form an amphipathic α-helix interacting with the second IL-17A monomer.	RESULTS
0	4	Pro6	residue_name_number	Pro6 of HAP makes a transition between the N-terminal β-strand and the C-terminal α-helix of HAP.	RESULTS
8	11	HAP	chemical	Pro6 of HAP makes a transition between the N-terminal β-strand and the C-terminal α-helix of HAP.	RESULTS
54	62	β-strand	structure_element	Pro6 of HAP makes a transition between the N-terminal β-strand and the C-terminal α-helix of HAP.	RESULTS
82	89	α-helix	structure_element	Pro6 of HAP makes a transition between the N-terminal β-strand and the C-terminal α-helix of HAP.	RESULTS
93	96	HAP	chemical	Pro6 of HAP makes a transition between the N-terminal β-strand and the C-terminal α-helix of HAP.	RESULTS
20	34	IL-17A/IL-17RA	complex_assembly	As a comparison, an IL-17A/IL-17RA complex structure (PDB code 4HSA) is also shown with IL-17A in the same orientation (Fig. 2C).	RESULTS
35	52	complex structure	evidence	As a comparison, an IL-17A/IL-17RA complex structure (PDB code 4HSA) is also shown with IL-17A in the same orientation (Fig. 2C).	RESULTS
88	94	IL-17A	protein	As a comparison, an IL-17A/IL-17RA complex structure (PDB code 4HSA) is also shown with IL-17A in the same orientation (Fig. 2C).	RESULTS
24	30	IL-17A	protein	Inhibition mechanism of IL-17A signaling by HAP	RESULTS
44	47	HAP	chemical	Inhibition mechanism of IL-17A signaling by HAP	RESULTS
0	7	IL-17RA	protein	IL-17RA binds IL-17A at three regions on the IL-17A homodimer.	RESULTS
14	20	IL-17A	protein	IL-17RA binds IL-17A at three regions on the IL-17A homodimer.	RESULTS
45	51	IL-17A	protein	IL-17RA binds IL-17A at three regions on the IL-17A homodimer.	RESULTS
52	61	homodimer	oligomeric_state	IL-17RA binds IL-17A at three regions on the IL-17A homodimer.	RESULTS
0	3	HAP	chemical	HAP binds IL-17A at region I. Region I is formed by residues at the ends of β strands 0 and 4, and from loops 1–2 and 3–4 of IL-17A (Fig. 2).	RESULTS
10	16	IL-17A	protein	HAP binds IL-17A at region I. Region I is formed by residues at the ends of β strands 0 and 4, and from loops 1–2 and 3–4 of IL-17A (Fig. 2).	RESULTS
20	28	region I	structure_element	HAP binds IL-17A at region I. Region I is formed by residues at the ends of β strands 0 and 4, and from loops 1–2 and 3–4 of IL-17A (Fig. 2).	RESULTS
30	38	Region I	structure_element	HAP binds IL-17A at region I. Region I is formed by residues at the ends of β strands 0 and 4, and from loops 1–2 and 3–4 of IL-17A (Fig. 2).	RESULTS
76	93	β strands 0 and 4	structure_element	HAP binds IL-17A at region I. Region I is formed by residues at the ends of β strands 0 and 4, and from loops 1–2 and 3–4 of IL-17A (Fig. 2).	RESULTS
104	113	loops 1–2	structure_element	HAP binds IL-17A at region I. Region I is formed by residues at the ends of β strands 0 and 4, and from loops 1–2 and 3–4 of IL-17A (Fig. 2).	RESULTS
118	121	3–4	structure_element	HAP binds IL-17A at region I. Region I is formed by residues at the ends of β strands 0 and 4, and from loops 1–2 and 3–4 of IL-17A (Fig. 2).	RESULTS
125	131	IL-17A	protein	HAP binds IL-17A at region I. Region I is formed by residues at the ends of β strands 0 and 4, and from loops 1–2 and 3–4 of IL-17A (Fig. 2).	RESULTS
26	34	region I	structure_element	Conformational changes in region I induced by HAP binding alone may allosterically affect IL-17RA binding, but more importantly, the α-helix of HAP directly competes with IL-17RA for binding to IL-17A (Fig. 3).	RESULTS
46	49	HAP	chemical	Conformational changes in region I induced by HAP binding alone may allosterically affect IL-17RA binding, but more importantly, the α-helix of HAP directly competes with IL-17RA for binding to IL-17A (Fig. 3).	RESULTS
90	97	IL-17RA	protein	Conformational changes in region I induced by HAP binding alone may allosterically affect IL-17RA binding, but more importantly, the α-helix of HAP directly competes with IL-17RA for binding to IL-17A (Fig. 3).	RESULTS
133	140	α-helix	structure_element	Conformational changes in region I induced by HAP binding alone may allosterically affect IL-17RA binding, but more importantly, the α-helix of HAP directly competes with IL-17RA for binding to IL-17A (Fig. 3).	RESULTS
144	147	HAP	chemical	Conformational changes in region I induced by HAP binding alone may allosterically affect IL-17RA binding, but more importantly, the α-helix of HAP directly competes with IL-17RA for binding to IL-17A (Fig. 3).	RESULTS
171	178	IL-17RA	protein	Conformational changes in region I induced by HAP binding alone may allosterically affect IL-17RA binding, but more importantly, the α-helix of HAP directly competes with IL-17RA for binding to IL-17A (Fig. 3).	RESULTS
194	200	IL-17A	protein	Conformational changes in region I induced by HAP binding alone may allosterically affect IL-17RA binding, but more importantly, the α-helix of HAP directly competes with IL-17RA for binding to IL-17A (Fig. 3).	RESULTS
46	53	α helix	structure_element	The most significant interactions between the α helix of HAP and IL-17A involve Trp12 of HAP, which binds in a hydrophobic pocket in IL-17A formed by the side chains of Phe110, Tyr62, Pro59 and the hydrophobic portion of the Arg101 side chain (Fig. 3A).	RESULTS
57	60	HAP	chemical	The most significant interactions between the α helix of HAP and IL-17A involve Trp12 of HAP, which binds in a hydrophobic pocket in IL-17A formed by the side chains of Phe110, Tyr62, Pro59 and the hydrophobic portion of the Arg101 side chain (Fig. 3A).	RESULTS
65	71	IL-17A	protein	The most significant interactions between the α helix of HAP and IL-17A involve Trp12 of HAP, which binds in a hydrophobic pocket in IL-17A formed by the side chains of Phe110, Tyr62, Pro59 and the hydrophobic portion of the Arg101 side chain (Fig. 3A).	RESULTS
80	85	Trp12	residue_name_number	The most significant interactions between the α helix of HAP and IL-17A involve Trp12 of HAP, which binds in a hydrophobic pocket in IL-17A formed by the side chains of Phe110, Tyr62, Pro59 and the hydrophobic portion of the Arg101 side chain (Fig. 3A).	RESULTS
89	92	HAP	chemical	The most significant interactions between the α helix of HAP and IL-17A involve Trp12 of HAP, which binds in a hydrophobic pocket in IL-17A formed by the side chains of Phe110, Tyr62, Pro59 and the hydrophobic portion of the Arg101 side chain (Fig. 3A).	RESULTS
111	129	hydrophobic pocket	site	The most significant interactions between the α helix of HAP and IL-17A involve Trp12 of HAP, which binds in a hydrophobic pocket in IL-17A formed by the side chains of Phe110, Tyr62, Pro59 and the hydrophobic portion of the Arg101 side chain (Fig. 3A).	RESULTS
133	139	IL-17A	protein	The most significant interactions between the α helix of HAP and IL-17A involve Trp12 of HAP, which binds in a hydrophobic pocket in IL-17A formed by the side chains of Phe110, Tyr62, Pro59 and the hydrophobic portion of the Arg101 side chain (Fig. 3A).	RESULTS
169	175	Phe110	residue_name_number	The most significant interactions between the α helix of HAP and IL-17A involve Trp12 of HAP, which binds in a hydrophobic pocket in IL-17A formed by the side chains of Phe110, Tyr62, Pro59 and the hydrophobic portion of the Arg101 side chain (Fig. 3A).	RESULTS
177	182	Tyr62	residue_name_number	The most significant interactions between the α helix of HAP and IL-17A involve Trp12 of HAP, which binds in a hydrophobic pocket in IL-17A formed by the side chains of Phe110, Tyr62, Pro59 and the hydrophobic portion of the Arg101 side chain (Fig. 3A).	RESULTS
184	189	Pro59	residue_name_number	The most significant interactions between the α helix of HAP and IL-17A involve Trp12 of HAP, which binds in a hydrophobic pocket in IL-17A formed by the side chains of Phe110, Tyr62, Pro59 and the hydrophobic portion of the Arg101 side chain (Fig. 3A).	RESULTS
225	231	Arg101	residue_name_number	The most significant interactions between the α helix of HAP and IL-17A involve Trp12 of HAP, which binds in a hydrophobic pocket in IL-17A formed by the side chains of Phe110, Tyr62, Pro59 and the hydrophobic portion of the Arg101 side chain (Fig. 3A).	RESULTS
4	9	Trp12	residue_name_number	The Trp12 side chain of HAP donates a hydrogen bond to the main chain oxygen of Pro69 of IL-17A.	RESULTS
24	27	HAP	chemical	The Trp12 side chain of HAP donates a hydrogen bond to the main chain oxygen of Pro69 of IL-17A.	RESULTS
38	51	hydrogen bond	bond_interaction	The Trp12 side chain of HAP donates a hydrogen bond to the main chain oxygen of Pro69 of IL-17A.	RESULTS
80	85	Pro69	residue_name_number	The Trp12 side chain of HAP donates a hydrogen bond to the main chain oxygen of Pro69 of IL-17A.	RESULTS
89	95	IL-17A	protein	The Trp12 side chain of HAP donates a hydrogen bond to the main chain oxygen of Pro69 of IL-17A.	RESULTS
23	29	Arg101	residue_name_number	The positively charged Arg101 side chain of the IL-17A engages in a charge-helix dipole interaction with the main chain oxygen of Trp12.	RESULTS
48	54	IL-17A	protein	The positively charged Arg101 side chain of the IL-17A engages in a charge-helix dipole interaction with the main chain oxygen of Trp12.	RESULTS
68	99	charge-helix dipole interaction	bond_interaction	The positively charged Arg101 side chain of the IL-17A engages in a charge-helix dipole interaction with the main chain oxygen of Trp12.	RESULTS
130	135	Trp12	residue_name_number	The positively charged Arg101 side chain of the IL-17A engages in a charge-helix dipole interaction with the main chain oxygen of Trp12.	RESULTS
14	18	Leu9	residue_name_number	Additionally, Leu9 and Ile13 of the HAP have hydrophobic interactions with IL-17A, and the Asp8 side chain has hydrogen bond and ion pair interactions with Tyr62 and Lys114 of IL-17A, respectively.	RESULTS
23	28	Ile13	residue_name_number	Additionally, Leu9 and Ile13 of the HAP have hydrophobic interactions with IL-17A, and the Asp8 side chain has hydrogen bond and ion pair interactions with Tyr62 and Lys114 of IL-17A, respectively.	RESULTS
36	39	HAP	chemical	Additionally, Leu9 and Ile13 of the HAP have hydrophobic interactions with IL-17A, and the Asp8 side chain has hydrogen bond and ion pair interactions with Tyr62 and Lys114 of IL-17A, respectively.	RESULTS
45	69	hydrophobic interactions	bond_interaction	Additionally, Leu9 and Ile13 of the HAP have hydrophobic interactions with IL-17A, and the Asp8 side chain has hydrogen bond and ion pair interactions with Tyr62 and Lys114 of IL-17A, respectively.	RESULTS
75	81	IL-17A	protein	Additionally, Leu9 and Ile13 of the HAP have hydrophobic interactions with IL-17A, and the Asp8 side chain has hydrogen bond and ion pair interactions with Tyr62 and Lys114 of IL-17A, respectively.	RESULTS
91	95	Asp8	residue_name_number	Additionally, Leu9 and Ile13 of the HAP have hydrophobic interactions with IL-17A, and the Asp8 side chain has hydrogen bond and ion pair interactions with Tyr62 and Lys114 of IL-17A, respectively.	RESULTS
111	124	hydrogen bond	bond_interaction	Additionally, Leu9 and Ile13 of the HAP have hydrophobic interactions with IL-17A, and the Asp8 side chain has hydrogen bond and ion pair interactions with Tyr62 and Lys114 of IL-17A, respectively.	RESULTS
129	150	ion pair interactions	bond_interaction	Additionally, Leu9 and Ile13 of the HAP have hydrophobic interactions with IL-17A, and the Asp8 side chain has hydrogen bond and ion pair interactions with Tyr62 and Lys114 of IL-17A, respectively.	RESULTS
156	161	Tyr62	residue_name_number	Additionally, Leu9 and Ile13 of the HAP have hydrophobic interactions with IL-17A, and the Asp8 side chain has hydrogen bond and ion pair interactions with Tyr62 and Lys114 of IL-17A, respectively.	RESULTS
166	172	Lys114	residue_name_number	Additionally, Leu9 and Ile13 of the HAP have hydrophobic interactions with IL-17A, and the Asp8 side chain has hydrogen bond and ion pair interactions with Tyr62 and Lys114 of IL-17A, respectively.	RESULTS
176	182	IL-17A	protein	Additionally, Leu9 and Ile13 of the HAP have hydrophobic interactions with IL-17A, and the Asp8 side chain has hydrogen bond and ion pair interactions with Tyr62 and Lys114 of IL-17A, respectively.	RESULTS
3	11	region I	structure_element	In region I, an IL-17RA peptide interacts with IL-17A in a very similar fashion to the α-helix of HAP.	RESULTS
16	23	IL-17RA	protein	In region I, an IL-17RA peptide interacts with IL-17A in a very similar fashion to the α-helix of HAP.	RESULTS
47	53	IL-17A	protein	In region I, an IL-17RA peptide interacts with IL-17A in a very similar fashion to the α-helix of HAP.	RESULTS
87	94	α-helix	structure_element	In region I, an IL-17RA peptide interacts with IL-17A in a very similar fashion to the α-helix of HAP.	RESULTS
98	101	HAP	chemical	In region I, an IL-17RA peptide interacts with IL-17A in a very similar fashion to the α-helix of HAP.	RESULTS
4	11	IL-17RA	protein	The IL-17RA peptide has sequences of 27LDDSWI, and part of the peptide is also α-helical (Fig. 3B).	RESULTS
37	45	27LDDSWI	chemical	The IL-17RA peptide has sequences of 27LDDSWI, and part of the peptide is also α-helical (Fig. 3B).	RESULTS
79	88	α-helical	structure_element	The IL-17RA peptide has sequences of 27LDDSWI, and part of the peptide is also α-helical (Fig. 3B).	RESULTS
0	4	Leu7	residue_name_number	Leu7, Trp31 and Ile32 of IL-17RA interact very similarly with the same residues of IL-17A as Leu9, Trp12 and Ile13 of HAP (Fig. 3B).	RESULTS
6	11	Trp31	residue_name_number	Leu7, Trp31 and Ile32 of IL-17RA interact very similarly with the same residues of IL-17A as Leu9, Trp12 and Ile13 of HAP (Fig. 3B).	RESULTS
16	21	Ile32	residue_name_number	Leu7, Trp31 and Ile32 of IL-17RA interact very similarly with the same residues of IL-17A as Leu9, Trp12 and Ile13 of HAP (Fig. 3B).	RESULTS
25	32	IL-17RA	protein	Leu7, Trp31 and Ile32 of IL-17RA interact very similarly with the same residues of IL-17A as Leu9, Trp12 and Ile13 of HAP (Fig. 3B).	RESULTS
83	89	IL-17A	protein	Leu7, Trp31 and Ile32 of IL-17RA interact very similarly with the same residues of IL-17A as Leu9, Trp12 and Ile13 of HAP (Fig. 3B).	RESULTS
93	97	Leu9	residue_name_number	Leu7, Trp31 and Ile32 of IL-17RA interact very similarly with the same residues of IL-17A as Leu9, Trp12 and Ile13 of HAP (Fig. 3B).	RESULTS
99	104	Trp12	residue_name_number	Leu7, Trp31 and Ile32 of IL-17RA interact very similarly with the same residues of IL-17A as Leu9, Trp12 and Ile13 of HAP (Fig. 3B).	RESULTS
109	114	Ile13	residue_name_number	Leu7, Trp31 and Ile32 of IL-17RA interact very similarly with the same residues of IL-17A as Leu9, Trp12 and Ile13 of HAP (Fig. 3B).	RESULTS
118	121	HAP	chemical	Leu7, Trp31 and Ile32 of IL-17RA interact very similarly with the same residues of IL-17A as Leu9, Trp12 and Ile13 of HAP (Fig. 3B).	RESULTS
19	26	α-helix	structure_element	In this sense, the α-helix of HAP with a sequence of 9LWDWI is a good mimetic of the 27LDDSWI peptide of IL-17RA.	RESULTS
30	33	HAP	chemical	In this sense, the α-helix of HAP with a sequence of 9LWDWI is a good mimetic of the 27LDDSWI peptide of IL-17RA.	RESULTS
53	59	9LWDWI	chemical	In this sense, the α-helix of HAP with a sequence of 9LWDWI is a good mimetic of the 27LDDSWI peptide of IL-17RA.	RESULTS
85	93	27LDDSWI	chemical	In this sense, the α-helix of HAP with a sequence of 9LWDWI is a good mimetic of the 27LDDSWI peptide of IL-17RA.	RESULTS
105	112	IL-17RA	protein	In this sense, the α-helix of HAP with a sequence of 9LWDWI is a good mimetic of the 27LDDSWI peptide of IL-17RA.	RESULTS
4	12	β-strand	structure_element	The β-strand of HAP has no equivalent in IL-17RA.	RESULTS
16	19	HAP	chemical	The β-strand of HAP has no equivalent in IL-17RA.	RESULTS
41	48	IL-17RA	protein	The β-strand of HAP has no equivalent in IL-17RA.	RESULTS
23	33	β-strand 0	structure_element	However, it mimics the β-strand 0 of IL-17A.	RESULTS
37	43	IL-17A	protein	However, it mimics the β-strand 0 of IL-17A.	RESULTS
4	15	amphipathic	protein_state	The amphipathic β-strand of HAP orients the hydrophilic side chains of His2 and Thr4 outwards, and the hydrophobic side chains of Ile1, Val3 and Ile5 inward (Fig. 3A).	RESULTS
16	24	β-strand	structure_element	The amphipathic β-strand of HAP orients the hydrophilic side chains of His2 and Thr4 outwards, and the hydrophobic side chains of Ile1, Val3 and Ile5 inward (Fig. 3A).	RESULTS
28	31	HAP	chemical	The amphipathic β-strand of HAP orients the hydrophilic side chains of His2 and Thr4 outwards, and the hydrophobic side chains of Ile1, Val3 and Ile5 inward (Fig. 3A).	RESULTS
71	75	His2	residue_name_number	The amphipathic β-strand of HAP orients the hydrophilic side chains of His2 and Thr4 outwards, and the hydrophobic side chains of Ile1, Val3 and Ile5 inward (Fig. 3A).	RESULTS
80	84	Thr4	residue_name_number	The amphipathic β-strand of HAP orients the hydrophilic side chains of His2 and Thr4 outwards, and the hydrophobic side chains of Ile1, Val3 and Ile5 inward (Fig. 3A).	RESULTS
130	134	Ile1	residue_name_number	The amphipathic β-strand of HAP orients the hydrophilic side chains of His2 and Thr4 outwards, and the hydrophobic side chains of Ile1, Val3 and Ile5 inward (Fig. 3A).	RESULTS
136	140	Val3	residue_name_number	The amphipathic β-strand of HAP orients the hydrophilic side chains of His2 and Thr4 outwards, and the hydrophobic side chains of Ile1, Val3 and Ile5 inward (Fig. 3A).	RESULTS
145	149	Ile5	residue_name_number	The amphipathic β-strand of HAP orients the hydrophilic side chains of His2 and Thr4 outwards, and the hydrophobic side chains of Ile1, Val3 and Ile5 inward (Fig. 3A).	RESULTS
0	10	β-strand 0	structure_element	β-strand 0 in IL-17A is also amphipathic with the sequence of 21TVMVNLNI.	RESULTS
14	20	IL-17A	protein	β-strand 0 in IL-17A is also amphipathic with the sequence of 21TVMVNLNI.	RESULTS
29	40	amphipathic	protein_state	β-strand 0 in IL-17A is also amphipathic with the sequence of 21TVMVNLNI.	RESULTS
62	72	21TVMVNLNI	chemical	β-strand 0 in IL-17A is also amphipathic with the sequence of 21TVMVNLNI.	RESULTS
7	13	IL-17A	protein	In all IL-17A structures obtained to date, β-strand 0 orients the hydrophilic side chains of Thr21, Asn25 and Asn27 outward, and the hydrophobic side chains of Val22, Val24, Leu26 and Ile28 inward.	RESULTS
14	24	structures	evidence	In all IL-17A structures obtained to date, β-strand 0 orients the hydrophilic side chains of Thr21, Asn25 and Asn27 outward, and the hydrophobic side chains of Val22, Val24, Leu26 and Ile28 inward.	RESULTS
43	53	β-strand 0	structure_element	In all IL-17A structures obtained to date, β-strand 0 orients the hydrophilic side chains of Thr21, Asn25 and Asn27 outward, and the hydrophobic side chains of Val22, Val24, Leu26 and Ile28 inward.	RESULTS
93	98	Thr21	residue_name_number	In all IL-17A structures obtained to date, β-strand 0 orients the hydrophilic side chains of Thr21, Asn25 and Asn27 outward, and the hydrophobic side chains of Val22, Val24, Leu26 and Ile28 inward.	RESULTS
100	105	Asn25	residue_name_number	In all IL-17A structures obtained to date, β-strand 0 orients the hydrophilic side chains of Thr21, Asn25 and Asn27 outward, and the hydrophobic side chains of Val22, Val24, Leu26 and Ile28 inward.	RESULTS
110	115	Asn27	residue_name_number	In all IL-17A structures obtained to date, β-strand 0 orients the hydrophilic side chains of Thr21, Asn25 and Asn27 outward, and the hydrophobic side chains of Val22, Val24, Leu26 and Ile28 inward.	RESULTS
160	165	Val22	residue_name_number	In all IL-17A structures obtained to date, β-strand 0 orients the hydrophilic side chains of Thr21, Asn25 and Asn27 outward, and the hydrophobic side chains of Val22, Val24, Leu26 and Ile28 inward.	RESULTS
167	172	Val24	residue_name_number	In all IL-17A structures obtained to date, β-strand 0 orients the hydrophilic side chains of Thr21, Asn25 and Asn27 outward, and the hydrophobic side chains of Val22, Val24, Leu26 and Ile28 inward.	RESULTS
174	179	Leu26	residue_name_number	In all IL-17A structures obtained to date, β-strand 0 orients the hydrophilic side chains of Thr21, Asn25 and Asn27 outward, and the hydrophobic side chains of Val22, Val24, Leu26 and Ile28 inward.	RESULTS
184	189	Ile28	residue_name_number	In all IL-17A structures obtained to date, β-strand 0 orients the hydrophilic side chains of Thr21, Asn25 and Asn27 outward, and the hydrophobic side chains of Val22, Val24, Leu26 and Ile28 inward.	RESULTS
4	18	binding pocket	site	The binding pocket occupied by either Trp12 of HAP or Trp31 of IL-17RA is not formed in the apo IL-17A structure (Fig. 3C).	RESULTS
38	43	Trp12	residue_name_number	The binding pocket occupied by either Trp12 of HAP or Trp31 of IL-17RA is not formed in the apo IL-17A structure (Fig. 3C).	RESULTS
47	50	HAP	chemical	The binding pocket occupied by either Trp12 of HAP or Trp31 of IL-17RA is not formed in the apo IL-17A structure (Fig. 3C).	RESULTS
54	59	Trp31	residue_name_number	The binding pocket occupied by either Trp12 of HAP or Trp31 of IL-17RA is not formed in the apo IL-17A structure (Fig. 3C).	RESULTS
63	70	IL-17RA	protein	The binding pocket occupied by either Trp12 of HAP or Trp31 of IL-17RA is not formed in the apo IL-17A structure (Fig. 3C).	RESULTS
92	95	apo	protein_state	The binding pocket occupied by either Trp12 of HAP or Trp31 of IL-17RA is not formed in the apo IL-17A structure (Fig. 3C).	RESULTS
96	102	IL-17A	protein	The binding pocket occupied by either Trp12 of HAP or Trp31 of IL-17RA is not formed in the apo IL-17A structure (Fig. 3C).	RESULTS
103	112	structure	evidence	The binding pocket occupied by either Trp12 of HAP or Trp31 of IL-17RA is not formed in the apo IL-17A structure (Fig. 3C).	RESULTS
26	32	IL-17A	protein	Conformational changes of IL-17A are needed for both HAP and IL-17RA to bind to that region.	RESULTS
53	56	HAP	chemical	Conformational changes of IL-17A are needed for both HAP and IL-17RA to bind to that region.	RESULTS
61	68	IL-17RA	protein	Conformational changes of IL-17A are needed for both HAP and IL-17RA to bind to that region.	RESULTS
17	20	HAP	chemical	Particularly for HAP, β-strands 0 have to shift out of the hydrophobic cleft formed by the main body of the IL-17A by as much as 10 Å between Cα atoms (Fig. 3C).	RESULTS
22	33	β-strands 0	structure_element	Particularly for HAP, β-strands 0 have to shift out of the hydrophobic cleft formed by the main body of the IL-17A by as much as 10 Å between Cα atoms (Fig. 3C).	RESULTS
59	76	hydrophobic cleft	site	Particularly for HAP, β-strands 0 have to shift out of the hydrophobic cleft formed by the main body of the IL-17A by as much as 10 Å between Cα atoms (Fig. 3C).	RESULTS
91	100	main body	structure_element	Particularly for HAP, β-strands 0 have to shift out of the hydrophobic cleft formed by the main body of the IL-17A by as much as 10 Å between Cα atoms (Fig. 3C).	RESULTS
108	114	IL-17A	protein	Particularly for HAP, β-strands 0 have to shift out of the hydrophobic cleft formed by the main body of the IL-17A by as much as 10 Å between Cα atoms (Fig. 3C).	RESULTS
19	22	apo	protein_state	Disruptions of the apo IL-17A structure by HAP binding are apparently compensated for by formation of the new interactions that involve almost the entire HAP molecule (Fig. 3B).	RESULTS
23	29	IL-17A	protein	Disruptions of the apo IL-17A structure by HAP binding are apparently compensated for by formation of the new interactions that involve almost the entire HAP molecule (Fig. 3B).	RESULTS
30	39	structure	evidence	Disruptions of the apo IL-17A structure by HAP binding are apparently compensated for by formation of the new interactions that involve almost the entire HAP molecule (Fig. 3B).	RESULTS
43	46	HAP	chemical	Disruptions of the apo IL-17A structure by HAP binding are apparently compensated for by formation of the new interactions that involve almost the entire HAP molecule (Fig. 3B).	RESULTS
154	157	HAP	chemical	Disruptions of the apo IL-17A structure by HAP binding are apparently compensated for by formation of the new interactions that involve almost the entire HAP molecule (Fig. 3B).	RESULTS
33	36	SAR	experimental_method	Structure basis for the observed SAR of peptides	RESULTS
4	14	IL-17A/HAP	complex_assembly	The IL-17A/HAP complex structure obtained is very consistent with the observed SAR of our identified peptide inhibitors, explaining well how the evolution of the initial phage peptide 1 to HAP and 45 improved its potency (Supplementary Figure S7).	RESULTS
15	32	complex structure	evidence	The IL-17A/HAP complex structure obtained is very consistent with the observed SAR of our identified peptide inhibitors, explaining well how the evolution of the initial phage peptide 1 to HAP and 45 improved its potency (Supplementary Figure S7).	RESULTS
79	82	SAR	experimental_method	The IL-17A/HAP complex structure obtained is very consistent with the observed SAR of our identified peptide inhibitors, explaining well how the evolution of the initial phage peptide 1 to HAP and 45 improved its potency (Supplementary Figure S7).	RESULTS
170	175	phage	experimental_method	The IL-17A/HAP complex structure obtained is very consistent with the observed SAR of our identified peptide inhibitors, explaining well how the evolution of the initial phage peptide 1 to HAP and 45 improved its potency (Supplementary Figure S7).	RESULTS
176	185	peptide 1	chemical	The IL-17A/HAP complex structure obtained is very consistent with the observed SAR of our identified peptide inhibitors, explaining well how the evolution of the initial phage peptide 1 to HAP and 45 improved its potency (Supplementary Figure S7).	RESULTS
189	192	HAP	chemical	The IL-17A/HAP complex structure obtained is very consistent with the observed SAR of our identified peptide inhibitors, explaining well how the evolution of the initial phage peptide 1 to HAP and 45 improved its potency (Supplementary Figure S7).	RESULTS
197	199	45	chemical	The IL-17A/HAP complex structure obtained is very consistent with the observed SAR of our identified peptide inhibitors, explaining well how the evolution of the initial phage peptide 1 to HAP and 45 improved its potency (Supplementary Figure S7).	RESULTS
37	42	Trp12	residue_name_number	The important interactions involving Trp12 of HAP explain the >90 times drop in potency of the W12A variant (6 vs 1, Table 1).	RESULTS
46	49	HAP	chemical	The important interactions involving Trp12 of HAP explain the >90 times drop in potency of the W12A variant (6 vs 1, Table 1).	RESULTS
95	99	W12A	mutant	The important interactions involving Trp12 of HAP explain the >90 times drop in potency of the W12A variant (6 vs 1, Table 1).	RESULTS
4	15	amphipathic	protein_state	The amphipathic nature of the HAP β-strand explains the preference of the hydrophilic residues at the 2 and 4 positions of peptides (14, 18, 19, 21 and 23 vs 1 and 22, Table 1).	RESULTS
30	33	HAP	chemical	The amphipathic nature of the HAP β-strand explains the preference of the hydrophilic residues at the 2 and 4 positions of peptides (14, 18, 19, 21 and 23 vs 1 and 22, Table 1).	RESULTS
34	42	β-strand	structure_element	The amphipathic nature of the HAP β-strand explains the preference of the hydrophilic residues at the 2 and 4 positions of peptides (14, 18, 19, 21 and 23 vs 1 and 22, Table 1).	RESULTS
102	103	2	residue_number	The amphipathic nature of the HAP β-strand explains the preference of the hydrophilic residues at the 2 and 4 positions of peptides (14, 18, 19, 21 and 23 vs 1 and 22, Table 1).	RESULTS
108	109	4	residue_number	The amphipathic nature of the HAP β-strand explains the preference of the hydrophilic residues at the 2 and 4 positions of peptides (14, 18, 19, 21 and 23 vs 1 and 22, Table 1).	RESULTS
133	135	14	chemical	The amphipathic nature of the HAP β-strand explains the preference of the hydrophilic residues at the 2 and 4 positions of peptides (14, 18, 19, 21 and 23 vs 1 and 22, Table 1).	RESULTS
137	139	18	chemical	The amphipathic nature of the HAP β-strand explains the preference of the hydrophilic residues at the 2 and 4 positions of peptides (14, 18, 19, 21 and 23 vs 1 and 22, Table 1).	RESULTS
141	143	19	chemical	The amphipathic nature of the HAP β-strand explains the preference of the hydrophilic residues at the 2 and 4 positions of peptides (14, 18, 19, 21 and 23 vs 1 and 22, Table 1).	RESULTS
145	147	21	chemical	The amphipathic nature of the HAP β-strand explains the preference of the hydrophilic residues at the 2 and 4 positions of peptides (14, 18, 19, 21 and 23 vs 1 and 22, Table 1).	RESULTS
152	154	23	chemical	The amphipathic nature of the HAP β-strand explains the preference of the hydrophilic residues at the 2 and 4 positions of peptides (14, 18, 19, 21 and 23 vs 1 and 22, Table 1).	RESULTS
158	159	1	chemical	The amphipathic nature of the HAP β-strand explains the preference of the hydrophilic residues at the 2 and 4 positions of peptides (14, 18, 19, 21 and 23 vs 1 and 22, Table 1).	RESULTS
164	166	22	chemical	The amphipathic nature of the HAP β-strand explains the preference of the hydrophilic residues at the 2 and 4 positions of peptides (14, 18, 19, 21 and 23 vs 1 and 22, Table 1).	RESULTS
27	30	HAP	chemical	All N-terminal residues of HAP are part of the β-sheet with β-stands 0 and 4 of IL-17A, which explains why removal of the first 1–3 residues completely abolishes the ability of HAP to block IL-17A cell signaling (31,32 and 33, Table 2).	RESULTS
47	54	β-sheet	structure_element	All N-terminal residues of HAP are part of the β-sheet with β-stands 0 and 4 of IL-17A, which explains why removal of the first 1–3 residues completely abolishes the ability of HAP to block IL-17A cell signaling (31,32 and 33, Table 2).	RESULTS
60	76	β-stands 0 and 4	structure_element	All N-terminal residues of HAP are part of the β-sheet with β-stands 0 and 4 of IL-17A, which explains why removal of the first 1–3 residues completely abolishes the ability of HAP to block IL-17A cell signaling (31,32 and 33, Table 2).	RESULTS
80	86	IL-17A	protein	All N-terminal residues of HAP are part of the β-sheet with β-stands 0 and 4 of IL-17A, which explains why removal of the first 1–3 residues completely abolishes the ability of HAP to block IL-17A cell signaling (31,32 and 33, Table 2).	RESULTS
107	117	removal of	experimental_method	All N-terminal residues of HAP are part of the β-sheet with β-stands 0 and 4 of IL-17A, which explains why removal of the first 1–3 residues completely abolishes the ability of HAP to block IL-17A cell signaling (31,32 and 33, Table 2).	RESULTS
122	140	first 1–3 residues	residue_range	All N-terminal residues of HAP are part of the β-sheet with β-stands 0 and 4 of IL-17A, which explains why removal of the first 1–3 residues completely abolishes the ability of HAP to block IL-17A cell signaling (31,32 and 33, Table 2).	RESULTS
177	180	HAP	chemical	All N-terminal residues of HAP are part of the β-sheet with β-stands 0 and 4 of IL-17A, which explains why removal of the first 1–3 residues completely abolishes the ability of HAP to block IL-17A cell signaling (31,32 and 33, Table 2).	RESULTS
190	196	IL-17A	protein	All N-terminal residues of HAP are part of the β-sheet with β-stands 0 and 4 of IL-17A, which explains why removal of the first 1–3 residues completely abolishes the ability of HAP to block IL-17A cell signaling (31,32 and 33, Table 2).	RESULTS
213	215	31	chemical	All N-terminal residues of HAP are part of the β-sheet with β-stands 0 and 4 of IL-17A, which explains why removal of the first 1–3 residues completely abolishes the ability of HAP to block IL-17A cell signaling (31,32 and 33, Table 2).	RESULTS
216	218	32	chemical	All N-terminal residues of HAP are part of the β-sheet with β-stands 0 and 4 of IL-17A, which explains why removal of the first 1–3 residues completely abolishes the ability of HAP to block IL-17A cell signaling (31,32 and 33, Table 2).	RESULTS
223	225	33	chemical	All N-terminal residues of HAP are part of the β-sheet with β-stands 0 and 4 of IL-17A, which explains why removal of the first 1–3 residues completely abolishes the ability of HAP to block IL-17A cell signaling (31,32 and 33, Table 2).	RESULTS
15	20	Asn14	residue_name_number	The C-terminal Asn14 and Lys15 of HAP are not directly involved in interactions with IL-17A, and this is reflected in the gradual reduction in activity caused by C-terminal truncations (35 and 36, Table 2).	RESULTS
25	30	Lys15	residue_name_number	The C-terminal Asn14 and Lys15 of HAP are not directly involved in interactions with IL-17A, and this is reflected in the gradual reduction in activity caused by C-terminal truncations (35 and 36, Table 2).	RESULTS
34	37	HAP	chemical	The C-terminal Asn14 and Lys15 of HAP are not directly involved in interactions with IL-17A, and this is reflected in the gradual reduction in activity caused by C-terminal truncations (35 and 36, Table 2).	RESULTS
85	91	IL-17A	protein	The C-terminal Asn14 and Lys15 of HAP are not directly involved in interactions with IL-17A, and this is reflected in the gradual reduction in activity caused by C-terminal truncations (35 and 36, Table 2).	RESULTS
173	184	truncations	experimental_method	The C-terminal Asn14 and Lys15 of HAP are not directly involved in interactions with IL-17A, and this is reflected in the gradual reduction in activity caused by C-terminal truncations (35 and 36, Table 2).	RESULTS
186	188	35	chemical	The C-terminal Asn14 and Lys15 of HAP are not directly involved in interactions with IL-17A, and this is reflected in the gradual reduction in activity caused by C-terminal truncations (35 and 36, Table 2).	RESULTS
193	195	36	chemical	The C-terminal Asn14 and Lys15 of HAP are not directly involved in interactions with IL-17A, and this is reflected in the gradual reduction in activity caused by C-terminal truncations (35 and 36, Table 2).	RESULTS
13	20	monomer	oligomeric_state	Each peptide monomer in 45 may not necessarily be more potent than HAP, but two monomer peptides within the same molecule that can simultaneously bind to IL-17A can greatly improve its potency due to avidity effects.	RESULTS
24	26	45	chemical	Each peptide monomer in 45 may not necessarily be more potent than HAP, but two monomer peptides within the same molecule that can simultaneously bind to IL-17A can greatly improve its potency due to avidity effects.	RESULTS
67	70	HAP	chemical	Each peptide monomer in 45 may not necessarily be more potent than HAP, but two monomer peptides within the same molecule that can simultaneously bind to IL-17A can greatly improve its potency due to avidity effects.	RESULTS
80	87	monomer	oligomeric_state	Each peptide monomer in 45 may not necessarily be more potent than HAP, but two monomer peptides within the same molecule that can simultaneously bind to IL-17A can greatly improve its potency due to avidity effects.	RESULTS
154	160	IL-17A	protein	Each peptide monomer in 45 may not necessarily be more potent than HAP, but two monomer peptides within the same molecule that can simultaneously bind to IL-17A can greatly improve its potency due to avidity effects.	RESULTS
0	3	HAP	chemical	HAP targets region I of IL-17A, an area that has the least sequence conservation in IL-17 cytokines.	RESULTS
12	20	region I	structure_element	HAP targets region I of IL-17A, an area that has the least sequence conservation in IL-17 cytokines.	RESULTS
24	30	IL-17A	protein	HAP targets region I of IL-17A, an area that has the least sequence conservation in IL-17 cytokines.	RESULTS
84	99	IL-17 cytokines	protein_type	HAP targets region I of IL-17A, an area that has the least sequence conservation in IL-17 cytokines.	RESULTS
42	58	HAP binding site	site	This lack of sequence conservation in the HAP binding site explains the observed specificity of HAP binding to human IL-17A.	RESULTS
96	99	HAP	chemical	This lack of sequence conservation in the HAP binding site explains the observed specificity of HAP binding to human IL-17A.	RESULTS
111	116	human	species	This lack of sequence conservation in the HAP binding site explains the observed specificity of HAP binding to human IL-17A.	RESULTS
117	123	IL-17A	protein	This lack of sequence conservation in the HAP binding site explains the observed specificity of HAP binding to human IL-17A.	RESULTS
41	47	IL-17F	protein	For example, inspection of the published IL-17F crystal structure (PDB code 1JPY) revealed a pocket of IL-17F similar to that of IL-17A for W12 of HAP binding, but it is occupied by a Phe-Phe motif at the N-terminal peptide of IL-17F.	RESULTS
48	65	crystal structure	evidence	For example, inspection of the published IL-17F crystal structure (PDB code 1JPY) revealed a pocket of IL-17F similar to that of IL-17A for W12 of HAP binding, but it is occupied by a Phe-Phe motif at the N-terminal peptide of IL-17F.	RESULTS
93	99	pocket	site	For example, inspection of the published IL-17F crystal structure (PDB code 1JPY) revealed a pocket of IL-17F similar to that of IL-17A for W12 of HAP binding, but it is occupied by a Phe-Phe motif at the N-terminal peptide of IL-17F.	RESULTS
103	109	IL-17F	protein	For example, inspection of the published IL-17F crystal structure (PDB code 1JPY) revealed a pocket of IL-17F similar to that of IL-17A for W12 of HAP binding, but it is occupied by a Phe-Phe motif at the N-terminal peptide of IL-17F.	RESULTS
129	135	IL-17A	protein	For example, inspection of the published IL-17F crystal structure (PDB code 1JPY) revealed a pocket of IL-17F similar to that of IL-17A for W12 of HAP binding, but it is occupied by a Phe-Phe motif at the N-terminal peptide of IL-17F.	RESULTS
140	143	W12	residue_name_number	For example, inspection of the published IL-17F crystal structure (PDB code 1JPY) revealed a pocket of IL-17F similar to that of IL-17A for W12 of HAP binding, but it is occupied by a Phe-Phe motif at the N-terminal peptide of IL-17F.	RESULTS
147	150	HAP	chemical	For example, inspection of the published IL-17F crystal structure (PDB code 1JPY) revealed a pocket of IL-17F similar to that of IL-17A for W12 of HAP binding, but it is occupied by a Phe-Phe motif at the N-terminal peptide of IL-17F.	RESULTS
184	197	Phe-Phe motif	structure_element	For example, inspection of the published IL-17F crystal structure (PDB code 1JPY) revealed a pocket of IL-17F similar to that of IL-17A for W12 of HAP binding, but it is occupied by a Phe-Phe motif at the N-terminal peptide of IL-17F.	RESULTS
227	233	IL-17F	protein	For example, inspection of the published IL-17F crystal structure (PDB code 1JPY) revealed a pocket of IL-17F similar to that of IL-17A for W12 of HAP binding, but it is occupied by a Phe-Phe motif at the N-terminal peptide of IL-17F.	RESULTS
5	18	Phe-Phe motif	structure_element	This Phe-Phe motif is missing in IL-17A.	RESULTS
22	29	missing	protein_state	This Phe-Phe motif is missing in IL-17A.	RESULTS
33	39	IL-17A	protein	This Phe-Phe motif is missing in IL-17A.	RESULTS
0	19	Sequence alignments	experimental_method	Sequence alignments between human and mouse IL-17A indicated that among IL-17A residues that interacting with HAP, majority differences occur in strand 0 of IL-17A which interacts with the N-terminal β-strand of HAP.	RESULTS
28	33	human	species	Sequence alignments between human and mouse IL-17A indicated that among IL-17A residues that interacting with HAP, majority differences occur in strand 0 of IL-17A which interacts with the N-terminal β-strand of HAP.	RESULTS
38	43	mouse	taxonomy_domain	Sequence alignments between human and mouse IL-17A indicated that among IL-17A residues that interacting with HAP, majority differences occur in strand 0 of IL-17A which interacts with the N-terminal β-strand of HAP.	RESULTS
44	50	IL-17A	protein	Sequence alignments between human and mouse IL-17A indicated that among IL-17A residues that interacting with HAP, majority differences occur in strand 0 of IL-17A which interacts with the N-terminal β-strand of HAP.	RESULTS
72	78	IL-17A	protein	Sequence alignments between human and mouse IL-17A indicated that among IL-17A residues that interacting with HAP, majority differences occur in strand 0 of IL-17A which interacts with the N-terminal β-strand of HAP.	RESULTS
110	113	HAP	chemical	Sequence alignments between human and mouse IL-17A indicated that among IL-17A residues that interacting with HAP, majority differences occur in strand 0 of IL-17A which interacts with the N-terminal β-strand of HAP.	RESULTS
145	153	strand 0	structure_element	Sequence alignments between human and mouse IL-17A indicated that among IL-17A residues that interacting with HAP, majority differences occur in strand 0 of IL-17A which interacts with the N-terminal β-strand of HAP.	RESULTS
157	163	IL-17A	protein	Sequence alignments between human and mouse IL-17A indicated that among IL-17A residues that interacting with HAP, majority differences occur in strand 0 of IL-17A which interacts with the N-terminal β-strand of HAP.	RESULTS
200	208	β-strand	structure_element	Sequence alignments between human and mouse IL-17A indicated that among IL-17A residues that interacting with HAP, majority differences occur in strand 0 of IL-17A which interacts with the N-terminal β-strand of HAP.	RESULTS
212	215	HAP	chemical	Sequence alignments between human and mouse IL-17A indicated that among IL-17A residues that interacting with HAP, majority differences occur in strand 0 of IL-17A which interacts with the N-terminal β-strand of HAP.	RESULTS
3	8	human	species	In human IL-17A the sequences are 21TVMVNLNI, and in mouse they are 21NVKVNLKV.	RESULTS
9	15	IL-17A	protein	In human IL-17A the sequences are 21TVMVNLNI, and in mouse they are 21NVKVNLKV.	RESULTS
34	44	21TVMVNLNI	chemical	In human IL-17A the sequences are 21TVMVNLNI, and in mouse they are 21NVKVNLKV.	RESULTS
53	58	mouse	taxonomy_domain	In human IL-17A the sequences are 21TVMVNLNI, and in mouse they are 21NVKVNLKV.	RESULTS
68	78	21NVKVNLKV	chemical	In human IL-17A the sequences are 21TVMVNLNI, and in mouse they are 21NVKVNLKV.	RESULTS
23	36	phage display	experimental_method	Using a combination of phage display and SAR we have discovered novel peptides that are IL-17A antagonists.	DISCUSS
41	44	SAR	experimental_method	Using a combination of phage display and SAR we have discovered novel peptides that are IL-17A antagonists.	DISCUSS
88	94	IL-17A	protein	Using a combination of phage display and SAR we have discovered novel peptides that are IL-17A antagonists.	DISCUSS
23	26	HAP	chemical	One of those peptides, HAP, also shows activity in inhibiting the production of multiple inflammatory cytokines by primary human keratinocytes stimulated by IL-17A and TNF-α, a disease relevant-model.	DISCUSS
102	111	cytokines	protein_type	One of those peptides, HAP, also shows activity in inhibiting the production of multiple inflammatory cytokines by primary human keratinocytes stimulated by IL-17A and TNF-α, a disease relevant-model.	DISCUSS
123	128	human	species	One of those peptides, HAP, also shows activity in inhibiting the production of multiple inflammatory cytokines by primary human keratinocytes stimulated by IL-17A and TNF-α, a disease relevant-model.	DISCUSS
157	163	IL-17A	protein	One of those peptides, HAP, also shows activity in inhibiting the production of multiple inflammatory cytokines by primary human keratinocytes stimulated by IL-17A and TNF-α, a disease relevant-model.	DISCUSS
168	173	TNF-α	protein	One of those peptides, HAP, also shows activity in inhibiting the production of multiple inflammatory cytokines by primary human keratinocytes stimulated by IL-17A and TNF-α, a disease relevant-model.	DISCUSS
13	23	determined	experimental_method	We have also determined the complex structure of IL-17A/HAP, which provides the structural basis for HAP’s antagonism to IL-17A signaling.	DISCUSS
28	45	complex structure	evidence	We have also determined the complex structure of IL-17A/HAP, which provides the structural basis for HAP’s antagonism to IL-17A signaling.	DISCUSS
49	59	IL-17A/HAP	complex_assembly	We have also determined the complex structure of IL-17A/HAP, which provides the structural basis for HAP’s antagonism to IL-17A signaling.	DISCUSS
101	104	HAP	chemical	We have also determined the complex structure of IL-17A/HAP, which provides the structural basis for HAP’s antagonism to IL-17A signaling.	DISCUSS
121	127	IL-17A	protein	We have also determined the complex structure of IL-17A/HAP, which provides the structural basis for HAP’s antagonism to IL-17A signaling.	DISCUSS
7	13	IL-17A	protein	During IL-17A signaling, IL-17A binds to one copy of IL-17RA and one copy of IL-17RC.	DISCUSS
25	31	IL-17A	protein	During IL-17A signaling, IL-17A binds to one copy of IL-17RA and one copy of IL-17RC.	DISCUSS
53	60	IL-17RA	protein	During IL-17A signaling, IL-17A binds to one copy of IL-17RA and one copy of IL-17RC.	DISCUSS
77	84	IL-17RC	protein	During IL-17A signaling, IL-17A binds to one copy of IL-17RA and one copy of IL-17RC.	DISCUSS
6	9	apo	protein_state	Since apo IL-17A is a homodimer with 2 fold symmetry, IL-17RA potentially can bind to either face of the IL-17A dimer.	DISCUSS
10	16	IL-17A	protein	Since apo IL-17A is a homodimer with 2 fold symmetry, IL-17RA potentially can bind to either face of the IL-17A dimer.	DISCUSS
22	31	homodimer	oligomeric_state	Since apo IL-17A is a homodimer with 2 fold symmetry, IL-17RA potentially can bind to either face of the IL-17A dimer.	DISCUSS
54	61	IL-17RA	protein	Since apo IL-17A is a homodimer with 2 fold symmetry, IL-17RA potentially can bind to either face of the IL-17A dimer.	DISCUSS
105	111	IL-17A	protein	Since apo IL-17A is a homodimer with 2 fold symmetry, IL-17RA potentially can bind to either face of the IL-17A dimer.	DISCUSS
112	117	dimer	oligomeric_state	Since apo IL-17A is a homodimer with 2 fold symmetry, IL-17RA potentially can bind to either face of the IL-17A dimer.	DISCUSS
9	12	HAP	chemical	With two HAP molecules covering both faces of the IL-17A dimer, HAP can block IL-17RA approaching from either face.	DISCUSS
50	56	IL-17A	protein	With two HAP molecules covering both faces of the IL-17A dimer, HAP can block IL-17RA approaching from either face.	DISCUSS
57	62	dimer	oligomeric_state	With two HAP molecules covering both faces of the IL-17A dimer, HAP can block IL-17RA approaching from either face.	DISCUSS
64	67	HAP	chemical	With two HAP molecules covering both faces of the IL-17A dimer, HAP can block IL-17RA approaching from either face.	DISCUSS
78	85	IL-17RA	protein	With two HAP molecules covering both faces of the IL-17A dimer, HAP can block IL-17RA approaching from either face.	DISCUSS
36	53	crystal structure	evidence	To form the 1:2 complex observed in crystal structure, it is important that there is no strong negative cooperativity in the binding of two HAP molecules.	DISCUSS
140	143	HAP	chemical	To form the 1:2 complex observed in crystal structure, it is important that there is no strong negative cooperativity in the binding of two HAP molecules.	DISCUSS
12	60	native electrospray ionization mass spectrometry	experimental_method	In fact, in native electrospray ionization mass spectrometry analysis only 1:2 IL-17A/HAP complex was observed even when IL-17A was in excess (Supplementary Figure S8), indicating a positive binding cooperativity that favors inhibition of IL-17RA binding by HAP.	DISCUSS
79	89	IL-17A/HAP	complex_assembly	In fact, in native electrospray ionization mass spectrometry analysis only 1:2 IL-17A/HAP complex was observed even when IL-17A was in excess (Supplementary Figure S8), indicating a positive binding cooperativity that favors inhibition of IL-17RA binding by HAP.	DISCUSS
121	127	IL-17A	protein	In fact, in native electrospray ionization mass spectrometry analysis only 1:2 IL-17A/HAP complex was observed even when IL-17A was in excess (Supplementary Figure S8), indicating a positive binding cooperativity that favors inhibition of IL-17RA binding by HAP.	DISCUSS
239	246	IL-17RA	protein	In fact, in native electrospray ionization mass spectrometry analysis only 1:2 IL-17A/HAP complex was observed even when IL-17A was in excess (Supplementary Figure S8), indicating a positive binding cooperativity that favors inhibition of IL-17RA binding by HAP.	DISCUSS
258	261	HAP	chemical	In fact, in native electrospray ionization mass spectrometry analysis only 1:2 IL-17A/HAP complex was observed even when IL-17A was in excess (Supplementary Figure S8), indicating a positive binding cooperativity that favors inhibition of IL-17RA binding by HAP.	DISCUSS
0	3	HAP	chemical	HAP, with only 15 residues, can achieve almost the same binding affinity as the much larger IL-17RA molecule, indicating a more efficient way of binding to IL-17A.	DISCUSS
15	26	15 residues	residue_range	HAP, with only 15 residues, can achieve almost the same binding affinity as the much larger IL-17RA molecule, indicating a more efficient way of binding to IL-17A.	DISCUSS
56	72	binding affinity	evidence	HAP, with only 15 residues, can achieve almost the same binding affinity as the much larger IL-17RA molecule, indicating a more efficient way of binding to IL-17A.	DISCUSS
92	99	IL-17RA	protein	HAP, with only 15 residues, can achieve almost the same binding affinity as the much larger IL-17RA molecule, indicating a more efficient way of binding to IL-17A.	DISCUSS
156	162	IL-17A	protein	HAP, with only 15 residues, can achieve almost the same binding affinity as the much larger IL-17RA molecule, indicating a more efficient way of binding to IL-17A.	DISCUSS
19	25	IL-17A	protein	The interaction of IL-17A with IL-17RA has an extensive interface, covering ~2,200 Å2 surface area of IL-17A.	DISCUSS
31	38	IL-17RA	protein	The interaction of IL-17A with IL-17RA has an extensive interface, covering ~2,200 Å2 surface area of IL-17A.	DISCUSS
56	65	interface	site	The interaction of IL-17A with IL-17RA has an extensive interface, covering ~2,200 Å2 surface area of IL-17A.	DISCUSS
102	108	IL-17A	protein	The interaction of IL-17A with IL-17RA has an extensive interface, covering ~2,200 Å2 surface area of IL-17A.	DISCUSS
39	71	IL-17A/IL-17RA binding interface	site	Due to the discontinuous nature of the IL-17A/IL-17RA binding interface, it is classified as having tertiary structural epitopes on both binding partners, and is therefore hard to target using small molecules.	DISCUSS
15	18	HAP	chemical	Our studies of HAP demonstrated an uncommon mode of action for a peptide in inhibiting such a difficult protein-protein interaction target, and suggest further possible improvements in its binding potency.	DISCUSS
29	32	HAP	chemical	One way of further improving HAP’s potency is by dimerization.	DISCUSS
21	24	HAP	chemical	Homo-dimerization of HAP (45) achieved sub-nanomolar potency against human IL-17A in cell assay.	DISCUSS
26	28	45	chemical	Homo-dimerization of HAP (45) achieved sub-nanomolar potency against human IL-17A in cell assay.	DISCUSS
69	74	human	species	Homo-dimerization of HAP (45) achieved sub-nanomolar potency against human IL-17A in cell assay.	DISCUSS
75	81	IL-17A	protein	Homo-dimerization of HAP (45) achieved sub-nanomolar potency against human IL-17A in cell assay.	DISCUSS
7	24	crystal structure	evidence	In the crystal structure, the distance between the carbonyl of Asn14 of one HAP molecule and the N-terminus of the second is only 15.7 Å, suggesting the potential for more potent dimeric peptides to be designed by using linkers of different lengths at different positions.	DISCUSS
63	68	Asn14	residue_name_number	In the crystal structure, the distance between the carbonyl of Asn14 of one HAP molecule and the N-terminus of the second is only 15.7 Å, suggesting the potential for more potent dimeric peptides to be designed by using linkers of different lengths at different positions.	DISCUSS
76	79	HAP	chemical	In the crystal structure, the distance between the carbonyl of Asn14 of one HAP molecule and the N-terminus of the second is only 15.7 Å, suggesting the potential for more potent dimeric peptides to be designed by using linkers of different lengths at different positions.	DISCUSS
179	186	dimeric	oligomeric_state	In the crystal structure, the distance between the carbonyl of Asn14 of one HAP molecule and the N-terminus of the second is only 15.7 Å, suggesting the potential for more potent dimeric peptides to be designed by using linkers of different lengths at different positions.	DISCUSS
187	195	peptides	chemical	In the crystal structure, the distance between the carbonyl of Asn14 of one HAP molecule and the N-terminus of the second is only 15.7 Å, suggesting the potential for more potent dimeric peptides to be designed by using linkers of different lengths at different positions.	DISCUSS
31	34	HAP	chemical	Another direction of improving HAP is by reducing its size.	DISCUSS
23	40	crystal structure	evidence	As demonstrated by the crystal structure, binding of the α-helix of HAP should be sufficient for preventing IL-17RA binding to IL-17A.	DISCUSS
57	64	α-helix	structure_element	As demonstrated by the crystal structure, binding of the α-helix of HAP should be sufficient for preventing IL-17RA binding to IL-17A.	DISCUSS
68	71	HAP	chemical	As demonstrated by the crystal structure, binding of the α-helix of HAP should be sufficient for preventing IL-17RA binding to IL-17A.	DISCUSS
108	115	IL-17RA	protein	As demonstrated by the crystal structure, binding of the α-helix of HAP should be sufficient for preventing IL-17RA binding to IL-17A.	DISCUSS
127	133	IL-17A	protein	As demonstrated by the crystal structure, binding of the α-helix of HAP should be sufficient for preventing IL-17RA binding to IL-17A.	DISCUSS
94	101	α-helix	structure_element	Theoretically, it is possible to design chemicals such as stapled α-helical peptides to block α-helix-mediated IL-17A/IL-17RA interactions.	DISCUSS
111	125	IL-17A/IL-17RA	complex_assembly	Theoretically, it is possible to design chemicals such as stapled α-helical peptides to block α-helix-mediated IL-17A/IL-17RA interactions.	DISCUSS
37	43	IL-17A	protein	In summary, these peptide-based anti-IL-17A modalities could be further developed as alternative therapeutic options to the reported monoclonal antibodies.	DISCUSS
144	154	antibodies	protein_type	In summary, these peptide-based anti-IL-17A modalities could be further developed as alternative therapeutic options to the reported monoclonal antibodies.	DISCUSS
67	73	IL-17A	protein	We are also very interested in finding non-peptidic small molecule IL-17A antagonists, and HAP can be used as an excellent tool peptide.	DISCUSS
91	94	HAP	chemical	We are also very interested in finding non-peptidic small molecule IL-17A antagonists, and HAP can be used as an excellent tool peptide.	DISCUSS
48	58	structures	evidence	The strategy utilized in generating the complex structures of HAP may also be useful for enabling structure based design of some known small molecule IL-17A antagonists.	DISCUSS
62	65	HAP	chemical	The strategy utilized in generating the complex structures of HAP may also be useful for enabling structure based design of some known small molecule IL-17A antagonists.	DISCUSS
11	14	HAP	chemical	Binding of HAP to IL-17A and inhibition of IL-17A/IL-17RA are measured by SPR, FRET and cell-based assays.	FIG
18	24	IL-17A	protein	Binding of HAP to IL-17A and inhibition of IL-17A/IL-17RA are measured by SPR, FRET and cell-based assays.	FIG
43	57	IL-17A/IL-17RA	complex_assembly	Binding of HAP to IL-17A and inhibition of IL-17A/IL-17RA are measured by SPR, FRET and cell-based assays.	FIG
74	77	SPR	experimental_method	Binding of HAP to IL-17A and inhibition of IL-17A/IL-17RA are measured by SPR, FRET and cell-based assays.	FIG
79	83	FRET	experimental_method	Binding of HAP to IL-17A and inhibition of IL-17A/IL-17RA are measured by SPR, FRET and cell-based assays.	FIG
88	105	cell-based assays	experimental_method	Binding of HAP to IL-17A and inhibition of IL-17A/IL-17RA are measured by SPR, FRET and cell-based assays.	FIG
12	15	SPR	experimental_method	(A) Typical SPR sensorgrams (black) of HAP at indicated concentrations binding to biotinylated human IL-17A immobilized on a streptavidin chip surface, fitted with single site binding model curves (red).	FIG
16	27	sensorgrams	evidence	(A) Typical SPR sensorgrams (black) of HAP at indicated concentrations binding to biotinylated human IL-17A immobilized on a streptavidin chip surface, fitted with single site binding model curves (red).	FIG
39	42	HAP	chemical	(A) Typical SPR sensorgrams (black) of HAP at indicated concentrations binding to biotinylated human IL-17A immobilized on a streptavidin chip surface, fitted with single site binding model curves (red).	FIG
82	94	biotinylated	protein_state	(A) Typical SPR sensorgrams (black) of HAP at indicated concentrations binding to biotinylated human IL-17A immobilized on a streptavidin chip surface, fitted with single site binding model curves (red).	FIG
95	100	human	species	(A) Typical SPR sensorgrams (black) of HAP at indicated concentrations binding to biotinylated human IL-17A immobilized on a streptavidin chip surface, fitted with single site binding model curves (red).	FIG
101	107	IL-17A	protein	(A) Typical SPR sensorgrams (black) of HAP at indicated concentrations binding to biotinylated human IL-17A immobilized on a streptavidin chip surface, fitted with single site binding model curves (red).	FIG
164	196	single site binding model curves	evidence	(A) Typical SPR sensorgrams (black) of HAP at indicated concentrations binding to biotinylated human IL-17A immobilized on a streptavidin chip surface, fitted with single site binding model curves (red).	FIG
20	22	ka	evidence	Kinetic parameters (ka, kd) were obtained by a global fit using three concentrations in triplicate.	FIG
24	26	kd	evidence	Kinetic parameters (ka, kd) were obtained by a global fit using three concentrations in triplicate.	FIG
0	2	KD	evidence	KD determined by the standard equation, KD = kd/ka. (B) HAP inhibits SPR signaling of IL-17A binding to immobilized IL-17RA.	FIG
40	42	KD	evidence	KD determined by the standard equation, KD = kd/ka. (B) HAP inhibits SPR signaling of IL-17A binding to immobilized IL-17RA.	FIG
45	47	kd	evidence	KD determined by the standard equation, KD = kd/ka. (B) HAP inhibits SPR signaling of IL-17A binding to immobilized IL-17RA.	FIG
48	50	ka	evidence	KD determined by the standard equation, KD = kd/ka. (B) HAP inhibits SPR signaling of IL-17A binding to immobilized IL-17RA.	FIG
56	59	HAP	chemical	KD determined by the standard equation, KD = kd/ka. (B) HAP inhibits SPR signaling of IL-17A binding to immobilized IL-17RA.	FIG
69	72	SPR	experimental_method	KD determined by the standard equation, KD = kd/ka. (B) HAP inhibits SPR signaling of IL-17A binding to immobilized IL-17RA.	FIG
86	92	IL-17A	protein	KD determined by the standard equation, KD = kd/ka. (B) HAP inhibits SPR signaling of IL-17A binding to immobilized IL-17RA.	FIG
104	115	immobilized	protein_state	KD determined by the standard equation, KD = kd/ka. (B) HAP inhibits SPR signaling of IL-17A binding to immobilized IL-17RA.	FIG
116	123	IL-17RA	protein	KD determined by the standard equation, KD = kd/ka. (B) HAP inhibits SPR signaling of IL-17A binding to immobilized IL-17RA.	FIG
96	102	IL-17A	protein	Data are mean and error bars of +/− standard deviation of three measurements. (C) Inhibition of IL-17A and IL-17RA binding by HAP measured by FRET assay.	FIG
107	114	IL-17RA	protein	Data are mean and error bars of +/− standard deviation of three measurements. (C) Inhibition of IL-17A and IL-17RA binding by HAP measured by FRET assay.	FIG
126	129	HAP	chemical	Data are mean and error bars of +/− standard deviation of three measurements. (C) Inhibition of IL-17A and IL-17RA binding by HAP measured by FRET assay.	FIG
142	152	FRET assay	experimental_method	Data are mean and error bars of +/− standard deviation of three measurements. (C) Inhibition of IL-17A and IL-17RA binding by HAP measured by FRET assay.	FIG
121	124	HAP	chemical	Data are mean and error bars of +/− standard deviation from 299 experiments, each performed in duplicate. (D) Example of HAP selective inhibition of the production of IL-8 (triangles), IL-6 (squares) and CCL-20 (circles) by primary human keratinocyte cells synergistically stimulated by 100 ng/ml IL-17A and 10 ng/ml TNF-α.	FIG
167	171	IL-8	protein_type	Data are mean and error bars of +/− standard deviation from 299 experiments, each performed in duplicate. (D) Example of HAP selective inhibition of the production of IL-8 (triangles), IL-6 (squares) and CCL-20 (circles) by primary human keratinocyte cells synergistically stimulated by 100 ng/ml IL-17A and 10 ng/ml TNF-α.	FIG
185	189	IL-6	protein_type	Data are mean and error bars of +/− standard deviation from 299 experiments, each performed in duplicate. (D) Example of HAP selective inhibition of the production of IL-8 (triangles), IL-6 (squares) and CCL-20 (circles) by primary human keratinocyte cells synergistically stimulated by 100 ng/ml IL-17A and 10 ng/ml TNF-α.	FIG
204	210	CCL-20	protein_type	Data are mean and error bars of +/− standard deviation from 299 experiments, each performed in duplicate. (D) Example of HAP selective inhibition of the production of IL-8 (triangles), IL-6 (squares) and CCL-20 (circles) by primary human keratinocyte cells synergistically stimulated by 100 ng/ml IL-17A and 10 ng/ml TNF-α.	FIG
232	237	human	species	Data are mean and error bars of +/− standard deviation from 299 experiments, each performed in duplicate. (D) Example of HAP selective inhibition of the production of IL-8 (triangles), IL-6 (squares) and CCL-20 (circles) by primary human keratinocyte cells synergistically stimulated by 100 ng/ml IL-17A and 10 ng/ml TNF-α.	FIG
297	303	IL-17A	protein	Data are mean and error bars of +/− standard deviation from 299 experiments, each performed in duplicate. (D) Example of HAP selective inhibition of the production of IL-8 (triangles), IL-6 (squares) and CCL-20 (circles) by primary human keratinocyte cells synergistically stimulated by 100 ng/ml IL-17A and 10 ng/ml TNF-α.	FIG
317	322	TNF-α	protein	Data are mean and error bars of +/− standard deviation from 299 experiments, each performed in duplicate. (D) Example of HAP selective inhibition of the production of IL-8 (triangles), IL-6 (squares) and CCL-20 (circles) by primary human keratinocyte cells synergistically stimulated by 100 ng/ml IL-17A and 10 ng/ml TNF-α.	FIG
0	3	HAP	chemical	HAP does not inhibit the baseline production of IL-6, IL-8 and CCL-20 stimulated by 10 ng/ml TNF-α alone (gray lines and symbols).	FIG
48	52	IL-6	protein_type	HAP does not inhibit the baseline production of IL-6, IL-8 and CCL-20 stimulated by 10 ng/ml TNF-α alone (gray lines and symbols).	FIG
54	58	IL-8	protein_type	HAP does not inhibit the baseline production of IL-6, IL-8 and CCL-20 stimulated by 10 ng/ml TNF-α alone (gray lines and symbols).	FIG
63	69	CCL-20	protein_type	HAP does not inhibit the baseline production of IL-6, IL-8 and CCL-20 stimulated by 10 ng/ml TNF-α alone (gray lines and symbols).	FIG
93	98	TNF-α	protein	HAP does not inhibit the baseline production of IL-6, IL-8 and CCL-20 stimulated by 10 ng/ml TNF-α alone (gray lines and symbols).	FIG
8	17	structure	evidence	Overall structure of the Fab/IL-17A/HAP complex in ribbon presentation.	FIG
25	39	Fab/IL-17A/HAP	complex_assembly	Overall structure of the Fab/IL-17A/HAP complex in ribbon presentation.	FIG
4	7	HAP	chemical	Two HAP molecules are colored blue and red, and IL-17A monomers are colored ice blue and pink, respectively.	FIG
48	54	IL-17A	protein	Two HAP molecules are colored blue and red, and IL-17A monomers are colored ice blue and pink, respectively.	FIG
55	63	monomers	oligomeric_state	Two HAP molecules are colored blue and red, and IL-17A monomers are colored ice blue and pink, respectively.	FIG
29	42	binding sites	site	(A) Overview of the distinct binding sites of Fab and HAP to IL-17A.	FIG
46	49	Fab	structure_element	(A) Overview of the distinct binding sites of Fab and HAP to IL-17A.	FIG
54	57	HAP	chemical	(A) Overview of the distinct binding sites of Fab and HAP to IL-17A.	FIG
61	67	IL-17A	protein	(A) Overview of the distinct binding sites of Fab and HAP to IL-17A.	FIG
25	35	IL-17A/HAP	complex_assembly	(B) Close-in view of the IL-17A/HAP structure.	FIG
36	45	structure	evidence	(B) Close-in view of the IL-17A/HAP structure.	FIG
0	6	IL-17A	protein	IL-17A β-strands are labelled.	FIG
7	16	β-strands	structure_element	IL-17A β-strands are labelled.	FIG
16	21	bound	protein_state	Each of the two bound HAP interacts with both monomers of the IL-17A dimer.	FIG
22	25	HAP	chemical	Each of the two bound HAP interacts with both monomers of the IL-17A dimer.	FIG
46	54	monomers	oligomeric_state	Each of the two bound HAP interacts with both monomers of the IL-17A dimer.	FIG
62	68	IL-17A	protein	Each of the two bound HAP interacts with both monomers of the IL-17A dimer.	FIG
69	74	dimer	oligomeric_state	Each of the two bound HAP interacts with both monomers of the IL-17A dimer.	FIG
25	39	IL-17A/IL-17RA	complex_assembly	(C) As a comparison, the IL-17A/IL-17RA complex was shown with IL-17A in the same orientation.	FIG
63	69	IL-17A	protein	(C) As a comparison, the IL-17A/IL-17RA complex was shown with IL-17A in the same orientation.	FIG
21	45	IL-17A/IL-17RA interface	site	Three distinct areas IL-17A/IL-17RA interface are labeled.	FIG
35	49	IL-17A/IL-17RA	complex_assembly	Mechanism of the inhibition of the IL-17A/IL-17RA interaction by HAP.	FIG
65	68	HAP	chemical	Mechanism of the inhibition of the IL-17A/IL-17RA interaction by HAP.	FIG
4	7	HAP	chemical	(A) HAP binds at region I of IL-17A.	FIG
17	25	region I	structure_element	(A) HAP binds at region I of IL-17A.	FIG
29	35	IL-17A	protein	(A) HAP binds at region I of IL-17A.	FIG
0	6	IL-17A	protein	IL-17A dimer is in surface presentation (β-strands 0 shown as ribbons for clarity).	FIG
7	12	dimer	oligomeric_state	IL-17A dimer is in surface presentation (β-strands 0 shown as ribbons for clarity).	FIG
41	52	β-strands 0	structure_element	IL-17A dimer is in surface presentation (β-strands 0 shown as ribbons for clarity).	FIG
0	18	Polar interactions	bond_interaction	Polar interactions are shown in dashes.	FIG
0	3	HAP	chemical	HAP residues as well as key IL-17A residues are labeled.	FIG
28	34	IL-17A	protein	HAP residues as well as key IL-17A residues are labeled.	FIG
19	22	HAP	chemical	For clarity, a few HAP residues are also shown in stick model with carbon atoms colored green, oxygen in red and nitrogen in blue.	FIG
4	10	I-17RA	protein	(B) I-17RA (ribbon in gold) peptide Leu27-Ile32 binds to the same area as the HAP α-helix.	FIG
36	47	Leu27-Ile32	residue_range	(B) I-17RA (ribbon in gold) peptide Leu27-Ile32 binds to the same area as the HAP α-helix.	FIG
78	81	HAP	chemical	(B) I-17RA (ribbon in gold) peptide Leu27-Ile32 binds to the same area as the HAP α-helix.	FIG
82	89	α-helix	structure_element	(B) I-17RA (ribbon in gold) peptide Leu27-Ile32 binds to the same area as the HAP α-helix.	FIG
0	5	Trp31	residue_name_number	Trp31 of IL-17RA binds to the same pocket in IL-17A as Trp12 of HAP. (C) As illustrated by overlay a single HAP molecule and β-strands 0 (grey) of the IL-17A/HAP complex in the apo IL-17A structure, conformational changes in region I of IL-17A are needed for binding of both the β-stand and α-helix of the HAP.	FIG
9	16	IL-17RA	protein	Trp31 of IL-17RA binds to the same pocket in IL-17A as Trp12 of HAP. (C) As illustrated by overlay a single HAP molecule and β-strands 0 (grey) of the IL-17A/HAP complex in the apo IL-17A structure, conformational changes in region I of IL-17A are needed for binding of both the β-stand and α-helix of the HAP.	FIG
35	41	pocket	site	Trp31 of IL-17RA binds to the same pocket in IL-17A as Trp12 of HAP. (C) As illustrated by overlay a single HAP molecule and β-strands 0 (grey) of the IL-17A/HAP complex in the apo IL-17A structure, conformational changes in region I of IL-17A are needed for binding of both the β-stand and α-helix of the HAP.	FIG
45	51	IL-17A	protein	Trp31 of IL-17RA binds to the same pocket in IL-17A as Trp12 of HAP. (C) As illustrated by overlay a single HAP molecule and β-strands 0 (grey) of the IL-17A/HAP complex in the apo IL-17A structure, conformational changes in region I of IL-17A are needed for binding of both the β-stand and α-helix of the HAP.	FIG
55	60	Trp12	residue_name_number	Trp31 of IL-17RA binds to the same pocket in IL-17A as Trp12 of HAP. (C) As illustrated by overlay a single HAP molecule and β-strands 0 (grey) of the IL-17A/HAP complex in the apo IL-17A structure, conformational changes in region I of IL-17A are needed for binding of both the β-stand and α-helix of the HAP.	FIG
64	67	HAP	chemical	Trp31 of IL-17RA binds to the same pocket in IL-17A as Trp12 of HAP. (C) As illustrated by overlay a single HAP molecule and β-strands 0 (grey) of the IL-17A/HAP complex in the apo IL-17A structure, conformational changes in region I of IL-17A are needed for binding of both the β-stand and α-helix of the HAP.	FIG
91	98	overlay	experimental_method	Trp31 of IL-17RA binds to the same pocket in IL-17A as Trp12 of HAP. (C) As illustrated by overlay a single HAP molecule and β-strands 0 (grey) of the IL-17A/HAP complex in the apo IL-17A structure, conformational changes in region I of IL-17A are needed for binding of both the β-stand and α-helix of the HAP.	FIG
108	111	HAP	chemical	Trp31 of IL-17RA binds to the same pocket in IL-17A as Trp12 of HAP. (C) As illustrated by overlay a single HAP molecule and β-strands 0 (grey) of the IL-17A/HAP complex in the apo IL-17A structure, conformational changes in region I of IL-17A are needed for binding of both the β-stand and α-helix of the HAP.	FIG
125	136	β-strands 0	structure_element	Trp31 of IL-17RA binds to the same pocket in IL-17A as Trp12 of HAP. (C) As illustrated by overlay a single HAP molecule and β-strands 0 (grey) of the IL-17A/HAP complex in the apo IL-17A structure, conformational changes in region I of IL-17A are needed for binding of both the β-stand and α-helix of the HAP.	FIG
151	161	IL-17A/HAP	complex_assembly	Trp31 of IL-17RA binds to the same pocket in IL-17A as Trp12 of HAP. (C) As illustrated by overlay a single HAP molecule and β-strands 0 (grey) of the IL-17A/HAP complex in the apo IL-17A structure, conformational changes in region I of IL-17A are needed for binding of both the β-stand and α-helix of the HAP.	FIG
177	180	apo	protein_state	Trp31 of IL-17RA binds to the same pocket in IL-17A as Trp12 of HAP. (C) As illustrated by overlay a single HAP molecule and β-strands 0 (grey) of the IL-17A/HAP complex in the apo IL-17A structure, conformational changes in region I of IL-17A are needed for binding of both the β-stand and α-helix of the HAP.	FIG
181	187	IL-17A	protein	Trp31 of IL-17RA binds to the same pocket in IL-17A as Trp12 of HAP. (C) As illustrated by overlay a single HAP molecule and β-strands 0 (grey) of the IL-17A/HAP complex in the apo IL-17A structure, conformational changes in region I of IL-17A are needed for binding of both the β-stand and α-helix of the HAP.	FIG
188	197	structure	evidence	Trp31 of IL-17RA binds to the same pocket in IL-17A as Trp12 of HAP. (C) As illustrated by overlay a single HAP molecule and β-strands 0 (grey) of the IL-17A/HAP complex in the apo IL-17A structure, conformational changes in region I of IL-17A are needed for binding of both the β-stand and α-helix of the HAP.	FIG
225	233	region I	structure_element	Trp31 of IL-17RA binds to the same pocket in IL-17A as Trp12 of HAP. (C) As illustrated by overlay a single HAP molecule and β-strands 0 (grey) of the IL-17A/HAP complex in the apo IL-17A structure, conformational changes in region I of IL-17A are needed for binding of both the β-stand and α-helix of the HAP.	FIG
237	243	IL-17A	protein	Trp31 of IL-17RA binds to the same pocket in IL-17A as Trp12 of HAP. (C) As illustrated by overlay a single HAP molecule and β-strands 0 (grey) of the IL-17A/HAP complex in the apo IL-17A structure, conformational changes in region I of IL-17A are needed for binding of both the β-stand and α-helix of the HAP.	FIG
279	286	β-stand	structure_element	Trp31 of IL-17RA binds to the same pocket in IL-17A as Trp12 of HAP. (C) As illustrated by overlay a single HAP molecule and β-strands 0 (grey) of the IL-17A/HAP complex in the apo IL-17A structure, conformational changes in region I of IL-17A are needed for binding of both the β-stand and α-helix of the HAP.	FIG
291	298	α-helix	structure_element	Trp31 of IL-17RA binds to the same pocket in IL-17A as Trp12 of HAP. (C) As illustrated by overlay a single HAP molecule and β-strands 0 (grey) of the IL-17A/HAP complex in the apo IL-17A structure, conformational changes in region I of IL-17A are needed for binding of both the β-stand and α-helix of the HAP.	FIG
306	309	HAP	chemical	Trp31 of IL-17RA binds to the same pocket in IL-17A as Trp12 of HAP. (C) As illustrated by overlay a single HAP molecule and β-strands 0 (grey) of the IL-17A/HAP complex in the apo IL-17A structure, conformational changes in region I of IL-17A are needed for binding of both the β-stand and α-helix of the HAP.	FIG
16	34	Trp binding pocket	site	Notice that the Trp binding pocket for W12 of HAP or W31 of IL-17RA is missing in the apo structure.	FIG
39	42	W12	residue_name_number	Notice that the Trp binding pocket for W12 of HAP or W31 of IL-17RA is missing in the apo structure.	FIG
46	49	HAP	chemical	Notice that the Trp binding pocket for W12 of HAP or W31 of IL-17RA is missing in the apo structure.	FIG
53	56	W31	residue_name_number	Notice that the Trp binding pocket for W12 of HAP or W31 of IL-17RA is missing in the apo structure.	FIG
60	67	IL-17RA	protein	Notice that the Trp binding pocket for W12 of HAP or W31 of IL-17RA is missing in the apo structure.	FIG
86	89	apo	protein_state	Notice that the Trp binding pocket for W12 of HAP or W31 of IL-17RA is missing in the apo structure.	FIG
90	99	structure	evidence	Notice that the Trp binding pocket for W12 of HAP or W31 of IL-17RA is missing in the apo structure.	FIG
0	26	ELISA competition activity	experimental_method	ELISA competition activity of peptide analogues of 1.	TABLE