6hg4: Difference between revisions
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<StructureSection load='6hg4' size='340' side='right'caption='[[6hg4]], [[Resolution|resolution]] 3.32Å' scene=''> | <StructureSection load='6hg4' size='340' side='right'caption='[[6hg4]], [[Resolution|resolution]] 3.32Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6hg4]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HG4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HG4 FirstGlance]. <br> | <table><tr><td colspan='2'>[[6hg4]] is a 2 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=6HG4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HG4 FirstGlance]. <br> | ||
</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=6hg4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hg4 OCA], [http://pdbe.org/6hg4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hg4 RCSB], [http://www.ebi.ac.uk/pdbsum/6hg4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hg4 ProSAT]</span></td></tr> | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL17F ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), IL17RC, UNQ6118/PRO20040/PRO38901 ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6hg4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hg4 OCA], [http://pdbe.org/6hg4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6hg4 RCSB], [http://www.ebi.ac.uk/pdbsum/6hg4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6hg4 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Disease == | == Disease == | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/IL17F_HUMAN IL17F_HUMAN]] Stimulates the production of other cytokines such as IL-6, IL-8 and granulocyte colony-stimulating factor, and can regulate cartilage matrix turnover. Stimulates PBMC and T-cell proliferation. Inhibits angiogenesis. [[http://www.uniprot.org/uniprot/I17RC_HUMAN I17RC_HUMAN]] Receptor for IL17A and IL17F homodimers as part of a heterodimeric complex with IL17RA (PubMed:16785495). Receptor for the heterodimer formed by IL17A and IL17B as part of a heterodimeric complex with IL17RA (PubMed:18684971). Has also been shown to be the cognate receptor for IL17F and to bind IL17A with high affinity without the need for IL17RA (PubMed:17911633). Activation of IL17RC leads to induction of expression of inflammatory chemokines and cytokines such as CXCL1 (PubMed:16785495).<ref>PMID:16785495</ref> <ref>PMID:17911633</ref> <ref>PMID:18684971</ref> Receptor for both IL17A and IL17F.<ref>PMID:16785495</ref> Does not bind IL17A or IL17F.<ref>PMID:16785495</ref> Does not bind IL17A or IL17F.<ref>PMID:16785495</ref> Receptor for both IL17A and IL17F.<ref>PMID:16785495</ref> | [[http://www.uniprot.org/uniprot/IL17F_HUMAN IL17F_HUMAN]] Stimulates the production of other cytokines such as IL-6, IL-8 and granulocyte colony-stimulating factor, and can regulate cartilage matrix turnover. Stimulates PBMC and T-cell proliferation. Inhibits angiogenesis. [[http://www.uniprot.org/uniprot/I17RC_HUMAN I17RC_HUMAN]] Receptor for IL17A and IL17F homodimers as part of a heterodimeric complex with IL17RA (PubMed:16785495). Receptor for the heterodimer formed by IL17A and IL17B as part of a heterodimeric complex with IL17RA (PubMed:18684971). Has also been shown to be the cognate receptor for IL17F and to bind IL17A with high affinity without the need for IL17RA (PubMed:17911633). Activation of IL17RC leads to induction of expression of inflammatory chemokines and cytokines such as CXCL1 (PubMed:16785495).<ref>PMID:16785495</ref> <ref>PMID:17911633</ref> <ref>PMID:18684971</ref> Receptor for both IL17A and IL17F.<ref>PMID:16785495</ref> Does not bind IL17A or IL17F.<ref>PMID:16785495</ref> Does not bind IL17A or IL17F.<ref>PMID:16785495</ref> Receptor for both IL17A and IL17F.<ref>PMID:16785495</ref> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Interleukin-17A (IL-17A), IL-17F, and IL-17A/F heterodimers are key cytokines of the innate and adaptive immune response. Dysregulation of the IL-17 pathway contributes to immune pathology, and it is therefore important to elucidate the molecular mechanisms that govern IL-17 recognition and signaling. The receptor IL-17RC is thought to act in concert with IL-17RA to transduce IL-17A-, IL-17F-, and IL-17A/F-mediated signals. We report the crystal structure of the extracellular domain of human IL-17RC in complex with IL-17F. In contrast to the expected model, we found that IL-17RC formed a symmetrical 2:1 complex with IL-17F, thus competing with IL-17RA for cytokine binding. Using biophysical techniques, we showed that IL-17A and IL-17A/F also form 2:1 complexes with IL-17RC, suggesting the possibility of IL-17RA-independent IL-17 signaling pathways. The crystal structure of the IL-17RC:IL-17F complex provides a structural basis for IL-17F signaling through IL-17RC, with potential therapeutic applications for respiratory allergy and inflammatory bowel diseases. | |||
Structural Analysis Reveals that the Cytokine IL-17F Forms a Homodimeric Complex with Receptor IL-17RC to Drive IL-17RA-Independent Signaling.,Goepfert A, Lehmann S, Blank J, Kolbinger F, Rondeau JM Immunity. 2020 Mar 17;52(3):499-512.e5. doi: 10.1016/j.immuni.2020.02.004. PMID:32187518<ref>PMID:32187518</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6hg4" style="background-color:#fffaf0;"></div> | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Goepfert, A]] | [[Category: Goepfert, A]] | ||
Revision as of 12:28, 1 April 2020
Crystal Structure of the human IL-17RC ECD in complex with human IL-17FCrystal Structure of the human IL-17RC ECD in complex with human IL-17F
Structural highlights
Disease[IL17F_HUMAN] Defects in IL17F are the cause of familial candidiasis type 6 (CANDF6) [MIM:613956]. CANDF6 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] [I17RC_HUMAN] Chronic mucocutaneous candidiasis. The disease is caused by mutations affecting the gene represented in this entry. Function[IL17F_HUMAN] Stimulates the production of other cytokines such as IL-6, IL-8 and granulocyte colony-stimulating factor, and can regulate cartilage matrix turnover. Stimulates PBMC and T-cell proliferation. Inhibits angiogenesis. [I17RC_HUMAN] Receptor for IL17A and IL17F homodimers as part of a heterodimeric complex with IL17RA (PubMed:16785495). Receptor for the heterodimer formed by IL17A and IL17B as part of a heterodimeric complex with IL17RA (PubMed:18684971). Has also been shown to be the cognate receptor for IL17F and to bind IL17A with high affinity without the need for IL17RA (PubMed:17911633). Activation of IL17RC leads to induction of expression of inflammatory chemokines and cytokines such as CXCL1 (PubMed:16785495).[2] [3] [4] Receptor for both IL17A and IL17F.[5] Does not bind IL17A or IL17F.[6] Does not bind IL17A or IL17F.[7] Receptor for both IL17A and IL17F.[8] Publication Abstract from PubMedInterleukin-17A (IL-17A), IL-17F, and IL-17A/F heterodimers are key cytokines of the innate and adaptive immune response. Dysregulation of the IL-17 pathway contributes to immune pathology, and it is therefore important to elucidate the molecular mechanisms that govern IL-17 recognition and signaling. The receptor IL-17RC is thought to act in concert with IL-17RA to transduce IL-17A-, IL-17F-, and IL-17A/F-mediated signals. We report the crystal structure of the extracellular domain of human IL-17RC in complex with IL-17F. In contrast to the expected model, we found that IL-17RC formed a symmetrical 2:1 complex with IL-17F, thus competing with IL-17RA for cytokine binding. Using biophysical techniques, we showed that IL-17A and IL-17A/F also form 2:1 complexes with IL-17RC, suggesting the possibility of IL-17RA-independent IL-17 signaling pathways. The crystal structure of the IL-17RC:IL-17F complex provides a structural basis for IL-17F signaling through IL-17RC, with potential therapeutic applications for respiratory allergy and inflammatory bowel diseases. Structural Analysis Reveals that the Cytokine IL-17F Forms a Homodimeric Complex with Receptor IL-17RC to Drive IL-17RA-Independent Signaling.,Goepfert A, Lehmann S, Blank J, Kolbinger F, Rondeau JM Immunity. 2020 Mar 17;52(3):499-512.e5. doi: 10.1016/j.immuni.2020.02.004. PMID:32187518[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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