5n92: Difference between revisions
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==Crystal Structure of Human IL-17AF== | |||
<StructureSection load='5n92' size='340' side='right'caption='[[5n92]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5n92]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5N92 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5N92 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=5n92 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n92 OCA], [https://pdbe.org/5n92 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5n92 RCSB], [https://www.ebi.ac.uk/pdbsum/5n92 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5n92 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[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;"> | |||
== Publication Abstract from PubMed == | |||
IL-17A and IL-17F are prominent members of the IL-17 family of cytokines that regulates both innate and adaptive immunity. IL-17A has been implicated in chronic inflammatory and autoimmune diseases, and anti-IL-17A antibodies have shown remarkable clinical efficacy in psoriasis and psoriatic arthritis patients. IL-17A and IL-17F are homodimeric cytokines that can also form the IL-17A/F heterodimer whose precise role in health and disease remains elusive. All three cytokines signal through the assembly of a ternary complex with the IL-17RA and IL-17RC receptors. Here we report the X-ray analysis of the human IL-17A/F heterodimer that reveals a two-faced cytokine closely mimicking IL-17A as well as IL-17F. We also present the crystal structure of its complex with the IL-17RA receptor. Unexpectedly in view of the much higher affinity of this receptor toward IL-17A, we find that IL-17RA is bound to the "F-face" of the heterodimer in the crystal. Using site-directed mutagenesis, we then demonstrate that IL-17RA can also bind to the "A-face" of IL-17A/F with similar affinity. Further, we show that IL-17RC does not discriminate between the two faces of the cytokine heterodimer either, thus enabling the formation of two topologically-distinct heterotrimeric complexes with potentially different signaling properties. | |||
The human IL-17A/F heterodimer: a two-faced cytokine with unique receptor recognition properties.,Goepfert A, Lehmann S, Wirth E, Rondeau JM Sci Rep. 2017 Aug 21;7(1):8906. doi: 10.1038/s41598-017-08360-9. PMID:28827714<ref>PMID:28827714</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5n92" style="background-color:#fffaf0;"></div> | ||
[[Category: Goepfert | |||
==See Also== | |||
*[[Interleukin 3D structures|Interleukin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Goepfert A]] | |||
[[Category: Rondeau J-M]] | |||
Latest revision as of 15:37, 15 November 2023
Crystal Structure of Human IL-17AFCrystal Structure of Human IL-17AF
Structural highlights
FunctionIL17_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 PubMedIL-17A and IL-17F are prominent members of the IL-17 family of cytokines that regulates both innate and adaptive immunity. IL-17A has been implicated in chronic inflammatory and autoimmune diseases, and anti-IL-17A antibodies have shown remarkable clinical efficacy in psoriasis and psoriatic arthritis patients. IL-17A and IL-17F are homodimeric cytokines that can also form the IL-17A/F heterodimer whose precise role in health and disease remains elusive. All three cytokines signal through the assembly of a ternary complex with the IL-17RA and IL-17RC receptors. Here we report the X-ray analysis of the human IL-17A/F heterodimer that reveals a two-faced cytokine closely mimicking IL-17A as well as IL-17F. We also present the crystal structure of its complex with the IL-17RA receptor. Unexpectedly in view of the much higher affinity of this receptor toward IL-17A, we find that IL-17RA is bound to the "F-face" of the heterodimer in the crystal. Using site-directed mutagenesis, we then demonstrate that IL-17RA can also bind to the "A-face" of IL-17A/F with similar affinity. Further, we show that IL-17RC does not discriminate between the two faces of the cytokine heterodimer either, thus enabling the formation of two topologically-distinct heterotrimeric complexes with potentially different signaling properties. The human IL-17A/F heterodimer: a two-faced cytokine with unique receptor recognition properties.,Goepfert A, Lehmann S, Wirth E, Rondeau JM Sci Rep. 2017 Aug 21;7(1):8906. doi: 10.1038/s41598-017-08360-9. PMID:28827714[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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