7uwn
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7uwn]] is a 7 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=7UWN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UWN FirstGlance]. <br> | <table><tr><td colspan='2'>[[7uwn]] is a 7 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=7UWN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UWN FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.01Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=7uwn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uwn OCA], [https://pdbe.org/7uwn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uwn RCSB], [https://www.ebi.ac.uk/pdbsum/7uwn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uwn ProSAT]</span></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=7uwn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uwn OCA], [https://pdbe.org/7uwn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uwn RCSB], [https://www.ebi.ac.uk/pdbsum/7uwn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uwn ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/I17RC_HUMAN I17RC_HUMAN] Chronic mucocutaneous candidiasis. The disease is caused by mutations affecting the gene represented in this entry. | ||
== Function == | == Function == | ||
| - | + | [https://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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
The IL-17 family of cytokines and receptors have central roles in host defence against infection and development of inflammatory diseases(1). The compositions and structures of functional IL-17 family ligand-receptor signalling assemblies remain unclear. IL-17E (also known as IL-25) is a key regulator of type 2 immune responses and driver of inflammatory diseases, such as allergic asthma, and requires both IL-17 receptor A (IL-17RA) and IL-17RB to elicit functional responses(2). Here we studied IL-25-IL-17RB binary and IL-25-IL-17RB-IL-17RA ternary complexes using a combination of cryo-electron microscopy, single-molecule imaging and cell-based signalling approaches. The IL-25-IL-17RB-IL-17RA ternary signalling assembly is a C2-symmetric complex in which the IL-25-IL-17RB homodimer is flanked by two 'wing-like' IL-17RA co-receptors through a 'tip-to-tip' geometry that is the key receptor-receptor interaction required for initiation of signal transduction. IL-25 interacts solely with IL-17RB to allosterically promote the formation of the IL-17RB-IL-17RA tip-to-tip interface. The resulting large separation between the receptors at the membrane-proximal level may reflect proximity constraints imposed by the intracellular domains for signalling. Cryo-electron microscopy structures of IL-17A-IL-17RA and IL-17A-IL-17RA-IL-17RC complexes reveal that this tip-to-tip architecture is a key organizing principle of the IL-17 receptor family. Furthermore, these studies reveal dual actions for IL-17RA sharing among IL-17 cytokine complexes, by either directly engaging IL-17 cytokines or alternatively functioning as a co-receptor. | The IL-17 family of cytokines and receptors have central roles in host defence against infection and development of inflammatory diseases(1). The compositions and structures of functional IL-17 family ligand-receptor signalling assemblies remain unclear. IL-17E (also known as IL-25) is a key regulator of type 2 immune responses and driver of inflammatory diseases, such as allergic asthma, and requires both IL-17 receptor A (IL-17RA) and IL-17RB to elicit functional responses(2). Here we studied IL-25-IL-17RB binary and IL-25-IL-17RB-IL-17RA ternary complexes using a combination of cryo-electron microscopy, single-molecule imaging and cell-based signalling approaches. The IL-25-IL-17RB-IL-17RA ternary signalling assembly is a C2-symmetric complex in which the IL-25-IL-17RB homodimer is flanked by two 'wing-like' IL-17RA co-receptors through a 'tip-to-tip' geometry that is the key receptor-receptor interaction required for initiation of signal transduction. IL-25 interacts solely with IL-17RB to allosterically promote the formation of the IL-17RB-IL-17RA tip-to-tip interface. The resulting large separation between the receptors at the membrane-proximal level may reflect proximity constraints imposed by the intracellular domains for signalling. Cryo-electron microscopy structures of IL-17A-IL-17RA and IL-17A-IL-17RA-IL-17RC complexes reveal that this tip-to-tip architecture is a key organizing principle of the IL-17 receptor family. Furthermore, these studies reveal dual actions for IL-17RA sharing among IL-17 cytokine complexes, by either directly engaging IL-17 cytokines or alternatively functioning as a co-receptor. | ||
| - | Organizing structural principles of the IL-17 ligand-receptor axis.,Wilson SC, Caveney NA, Yen M, Pollmann C, Xiang X, Jude KM, Hafer M, Tsutsumi N, Piehler J, Garcia KC Nature. 2022 | + | Organizing structural principles of the IL-17 ligand-receptor axis.,Wilson SC, Caveney NA, Yen M, Pollmann C, Xiang X, Jude KM, Hafer M, Tsutsumi N, Piehler J, Garcia KC Nature. 2022 Sep;609(7927):622-629. doi: 10.1038/s41586-022-05116-y. Epub 2022 , Jul 21. PMID:35863378<ref>PMID:35863378</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 7uwn" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 7uwn" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Interleukin 3D structures|Interleukin 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Structure of the IL-17A-IL-17RA-IL-17RC ternary complex
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