5nan: Difference between revisions
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==Crystal Structure of human IL-17AF in complex with human IL-17RA== | ==Crystal Structure of human IL-17AF in complex with human IL-17RA== | ||
<StructureSection load='5nan' size='340' side='right' caption='[[5nan]], [[Resolution|resolution]] 3.30Å' scene=''> | <StructureSection load='5nan' size='340' side='right'caption='[[5nan]], [[Resolution|resolution]] 3.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5nan]] is a 6 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5nan]] is a 6 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=5NAN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NAN FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.3Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | |||
<tr id=' | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5nan FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nan OCA], [https://pdbe.org/5nan PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nan RCSB], [https://www.ebi.ac.uk/pdbsum/5nan PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nan ProSAT]</span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Disease == | == Disease == | ||
[ | [https://www.uniprot.org/uniprot/I17RA_HUMAN I17RA_HUMAN] Defects in IL17RA are the cause of familial candidiasis type 5 (CANDF5) [MIM:[https://omim.org/entry/613953 613953]. CANDF5 is a rare disorder with altered immune responses and impaired clearance of fungal infections, selective against Candida. It is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida, mainly Candida albicans.<ref>PMID:21350122</ref> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/I17RA_HUMAN I17RA_HUMAN] Receptor for IL17A, IL17F and, in dimer with IL17RE, for IL17C. Binds its IL17A ligand with low affinity, suggesting that additional components are involved in IL17A-induced signaling.<ref>PMID:21993848</ref> <ref>PMID:19838198</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 22: | Line 21: | ||
</div> | </div> | ||
<div class="pdbe-citations 5nan" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5nan" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Interleukin 3D structures|Interleukin 3D structures]] | |||
*[[Interleukin receptor 3D structures|Interleukin receptor 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Goepfert A]] | ||
[[Category: | [[Category: Rondeau J-M]] | ||
Revision as of 15:43, 15 November 2023
Crystal Structure of human IL-17AF in complex with human IL-17RACrystal Structure of human IL-17AF in complex with human IL-17RA
Structural highlights
DiseaseI17RA_HUMAN Defects in IL17RA are the cause of familial candidiasis type 5 (CANDF5) [MIM:613953. CANDF5 is a rare disorder with altered immune responses and impaired clearance of fungal infections, selective against Candida. It is characterized by persistent and/or recurrent infections of the skin, nails and mucous membranes caused by organisms of the genus Candida, mainly Candida albicans.[1] FunctionI17RA_HUMAN Receptor for IL17A, IL17F and, in dimer with IL17RE, for IL17C. Binds its IL17A ligand with low affinity, suggesting that additional components are involved in IL17A-induced signaling.[2] [3] 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[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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