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| | ==Inhibiting complex IL-17A and IL-17RA interactions with a linear peptide== | | ==Inhibiting complex IL-17A and IL-17RA interactions with a linear peptide== |
| - | <StructureSection load='5hhx' size='340' side='right' caption='[[5hhx]], [[Resolution|resolution]] 3.00Å' scene=''> | + | <StructureSection load='5hhx' size='340' side='right'caption='[[5hhx]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5hhx]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HHX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HHX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5hhx]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HHX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HHX FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5hhv|5hhv]], [[5hi3|5hi3]], [[5hi4|5hi4]], [[5hi5|5hi5]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL17A, CTLA8, IL17 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5hhx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hhx OCA], [https://pdbe.org/5hhx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hhx RCSB], [https://www.ebi.ac.uk/pdbsum/5hhx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hhx ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5hhx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hhx OCA], [http://pdbe.org/5hhx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hhx RCSB], [http://www.ebi.ac.uk/pdbsum/5hhx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hhx ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IL17_HUMAN IL17_HUMAN]] Induces stromal cells to produce proinflammatory and hematopoietic cytokines. Enhances the surface expression of ICAM1/intracellular adhesion molecule 1 in fibroblasts. | + | [https://www.uniprot.org/uniprot/IL17_HUMAN IL17_HUMAN] Induces stromal cells to produce proinflammatory and hematopoietic cytokines. Enhances the surface expression of ICAM1/intracellular adhesion molecule 1 in fibroblasts. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5hhx" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5hhx" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Interleukin 3D structures|Interleukin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Liu, S]] | + | [[Category: Large Structures]] |
| - | [[Category: Complex crystal structure]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Il-17]] | + | [[Category: Liu S]] |
| - | [[Category: Immune system-inhibitor complex]]
| + | |
| - | [[Category: Inflammation]]
| + | |
| - | [[Category: Inhibitor]]
| + | |
| Structural highlights
Function
IL17_HUMAN Induces stromal cells to produce proinflammatory and hematopoietic cytokines. Enhances the surface expression of ICAM1/intracellular adhesion molecule 1 in fibroblasts.
Publication Abstract from PubMed
IL-17A is a pro-inflammatory cytokine that has been implicated in autoimmune and inflammatory diseases. Monoclonal antibodies inhibiting IL-17A signaling have demonstrated remarkable efficacy, but an oral therapy is still lacking. 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. HAP binds specifically to IL-17A and inhibits the interaction of the cytokine with its receptor, IL-17RA. Tested in primary human cells, HAP blocked the production of multiple inflammatory cytokines. Crystal structure studies revealed that two HAP molecules bind to one IL-17A dimer symmetrically. The N-terminal portions of HAP form a beta-strand that inserts between two IL-17A monomers while the C-terminal section forms an alpha helix that directly blocks IL-17RA from binding to the same region of IL-17A. This mode of inhibition suggests opportunities for developing peptide antagonists against this challenging target.
Inhibiting complex IL-17A and IL-17RA interactions with a linear peptide.,Liu S, Desharnais J, Sahasrabudhe PV, Jin P, Li W, Oates BD, Shanker S, Banker ME, Chrunyk BA, Song X, Feng X, Griffor M, Jimenez J, Chen G, Tumelty D, Bhat A, Bradshaw CW, Woodnutt G, Lappe RW, Thorarensen A, Qiu X, Withka JM, Wood LD Sci Rep. 2016 May 17;6:26071. doi: 10.1038/srep26071. PMID:27184415[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Liu S, Desharnais J, Sahasrabudhe PV, Jin P, Li W, Oates BD, Shanker S, Banker ME, Chrunyk BA, Song X, Feng X, Griffor M, Jimenez J, Chen G, Tumelty D, Bhat A, Bradshaw CW, Woodnutt G, Lappe RW, Thorarensen A, Qiu X, Withka JM, Wood LD. Inhibiting complex IL-17A and IL-17RA interactions with a linear peptide. Sci Rep. 2016 May 17;6:26071. doi: 10.1038/srep26071. PMID:27184415 doi:http://dx.doi.org/10.1038/srep26071
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