9vp0

Structural insights into IL-31 signaling inhibition by a neutralization antibody

spinqualitylabelsall models 9vp0, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9vp0 is a 3 chain structure with sequence from Canis lupus familiaris. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function C7G0W1_CANLF 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA