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==Structure of the higher-order IL-25-IL-17RB complex==
<StructureSection load='7uwk' size='340' side='right'caption='[[7uwk]], [[Resolution|resolution]] 4.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7uwk]] is a 12 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=7UWK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7UWK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.4&#8491;</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=7uwk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7uwk OCA], [https://pdbe.org/7uwk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7uwk RCSB], [https://www.ebi.ac.uk/pdbsum/7uwk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7uwk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/IL25_HUMAN IL25_HUMAN] Cytokine produced by various cells such as eosinophils, T-helper type 2 (Th2) cells or epithelial cells that plays a role in internal safety of adaptive immune responses by regulating cytokine production (PubMed:15860795, PubMed:25821217). Promotes and augments T-helper type 2 responses locally or systemically (PubMed:25821217). Exerts its activity via its receptor composed of IL17RA and IL17RB for signal transduction (By similarity). In turn, stimulates the JAK2-STAT5A pathway and promotes the secretion of type-2 associated cytokines including IL4, IL9 and IL13 (PubMed:25821217). Induces also the release of IL8, and IL6 from eosinophils through the combined activation of MAPK and NF-kappa-B pathways (PubMed:15860795). Inhibits the differentiation of T-helper (Th17) cells via the production of IL4, IL5 and IL13 (PubMed:11754819).[UniProtKB:Q8VHH8]<ref>PMID:11754819</ref> <ref>PMID:15860795</ref> <ref>PMID:25821217</ref> 
<div style="background-color:#fffaf0;">
== 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.

,  PMID:35863378<ref>PMID:35863378</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7uwk" style="background-color:#fffaf0;"></div>

==See Also==
*[[Interleukin 3D structures|Interleukin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Caveney NA]]
[[Category: Garcia KC]]
[[Category: Jude KM]]
[[Category: Wilson SC]]