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+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