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Updated: Aug 26, 2026

An ELISA Based Binding and Competition Method to Rapidly Determine Ligand-receptor Interactions
Published on: March 14, 2016
Cryo-EM structure of the interleukin-31 receptor complex defines non-canonical interactions that confer receptor
Yong Feng1, Gaofei Qian2, Zichu Wei2
1Department of Oncology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Engineering Research Center of Protein and Peptide Medicine, Ministry of Education, Nanjing 210023, China; Institute of Artificial Intelligence Biomedicine, Nanjing University, Nanjing, China.
Abstract:
Interleukin-31 (IL-31) is a Th2-associated cytokine that induces inflammatory and pruritic diseases through a heterodimeric receptor composed of IL-31Rα and OSMRβ. Although IL-31 has emerged as an important therapeutic target, the molecular mechanism by which IL-31 engages IL-31Rα and OSMRβ to assemble its receptor complex remains poorly defined. Here we report a 3.3 Å cryo-EM structure of the human IL-31/IL-31Rα/OSMRβ complex. The structure reveals that IL-31 assembles its receptors through a site 2-site 3 architecture reminiscent of LIF and OSM, yet employs distinct receptor-recognition features at both interfaces. Site 2 is dominated by a hydrophilic IL-31-IL-31Rα interface that lacks the aromatic anchoring mode observed in LIF and OSM receptor complexes, whereas site 3 adopts a remodeled anchoring mode involving IL-31 K134, T130, and the conserved OSMRβ W267 anchor. Structure-guided mutagenesis and SPR binding analyses support the contributions of site 2 and site 3 interface residues to receptor recognition. Together, these findings reveal how non-canonical interactions at sites 2 and 3 confer receptor specificity within the IL-31 receptor complex.
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