9UK5

crystal structure of the complex of interleukin-31 and its antibody

Summary for 9UK5

• Entry DOI: 10.2210/pdb9uk5/pdb
• Descriptor: Interleukin 31, Antibody-H, Antibody-L, ... (4 entities in total)
• Functional Keywords: cytokine; signaling pathway; interleukin, cytokine/immune system, cytokine-immune system complex
• Biological source: Canis lupus familiaris (Dog, Canis familiaris); More
• Total number of polymer chains: 3
• Total formula weight: 64678.81

Authors

Guo, T.,Gao, F.,Xiao, H. (deposition date: 2025-04-17, release date: 2025-10-29)

Primary citation

Guo, T.,Zheng, Y.,Fan, Z.,Liu, P.,Chai, Y.,Liao, X.,Zhang, C.,Pang, X.,Li, D.,Gao, F.,Xiao, H.
Structural insights into IL-31 signaling inhibition by a neutralizing antibody.
Structure, 2025

PubMed Abstract: Interleukin-31 (IL-31) signals through the IL-31 receptor alpha (IL-31RA) and oncostatin M receptor beta (OSMRβ) 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 OSMRβ (cOSMRβ) 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 α-helical A, α-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 cOSMRβ. In summary, this study reports the IL-31 structure, revealing a four-α-helical bundle cytokine, and elucidates 2D10-2's neutralizing mechanism by targeting the cIL-31-cOSMRβ interaction. These findings advance our understanding of IL-31 and offer insights for developing IL-31-targeted therapeutics.

PubMed: 41015037
DOI: 10.1016/j.str.2025.09.002

Experimental method

X-RAY DIFFRACTION (1.9 Å)