9vp0: Difference between revisions
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==Structural insights into IL-31 signaling inhibition by a neutralization antibody== | |||
<StructureSection load='9vp0' size='340' side='right'caption='[[9vp0]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9vp0]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Canis_lupus_familiaris Canis lupus familiaris]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9VP0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9VP0 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]] 2.1Å</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=9vp0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9vp0 OCA], [https://pdbe.org/9vp0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9vp0 RCSB], [https://www.ebi.ac.uk/pdbsum/9vp0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9vp0 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/C7G0W1_CANLF C7G0W1_CANLF] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Interleukin-31 (IL-31) signals through the IL-31 receptor alpha (IL-31RA) and oncostatin M receptor beta (OSMRbeta) heterodimer, mediating pruritus, dermatitis, inflammatory responses, neuroimmune interactions, and certain cancers. Here, we present the crystal structure of canine IL-31 (cIL-31) in complex with a neutralizing caninized monoclonal antibody (2D10-2). This antibody competitively inhibited cIL-31 binding to canine OSMRbeta (cOSMRbeta) but not to canine IL-31RA (cIL-31RA). Moreover, it effectively blocked cIL-31-induced STAT5 phosphorylation in vitro and alleviated cIL-31-induced pruritus in beagle dogs. Structural analysis identified key antibody-binding residues in alpha-helical A, alpha-helical D, and the AB loop of cIL-31. Systematic mutagenesis based on the complex structure further defined the conformational epitopes of cIL-31 recognized by cOSMRbeta. In summary, this study reports the IL-31 structure, revealing a four-alpha-helical bundle cytokine, and elucidates 2D10-2's neutralizing mechanism by targeting the cIL-31-cOSMRbeta interaction. These findings advance our understanding of IL-31 and offer insights for developing IL-31-targeted therapeutics. | |||
Structural insights into IL-31 signaling inhibition by a neutralizing antibody.,Guo T, Zheng Y, Fan Z, Liu P, Chai Y, Liao X, Zhang C, Pang X, Li D, Gao F, Xiao H Structure. 2025 Sep 26:S0969-2126(25)00345-4. doi: 10.1016/j.str.2025.09.002. PMID:41015037<ref>PMID:41015037</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Gao | <div class="pdbe-citations 9vp0" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Canis lupus familiaris]] | |||
[[Category: Large Structures]] | |||
[[Category: Gao F]] | |||
[[Category: Guo T]] | |||
[[Category: Xiao H]] | |||
Latest revision as of 07:30, 29 October 2025
Structural insights into IL-31 signaling inhibition by a neutralization antibody
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