Structure and Mechanism of Receptoe Sharing by the IL-10R2 Common Chain

Journal Article · Mon Jun 14 00:00:00 EDT 2010 · Structure

DOI:https://doi.org/10.1016/j.str.2010.02.009· OSTI ID:1002452

Yoon, Sung-il; Jones, Brandi C; Logsdon, Naomi J; Harris, Bethany D; Deshpande, Ashlesha; Radaeva, Svetlana; Halloran, Brian A; Gao, Bin; Walter, Mark R ^[1]

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1. NIH

IL-10R2 is a shared cell surface receptor required for the activation of five class 2 cytokines (IL-10, IL-22, IL-26, IL-28, and IL-29) that play critical roles in host defense. To define the molecular mechanisms that regulate its promiscuous binding, we have determined the crystal structure of the IL-10R2 ectodomain at 2.14 {angstrom} resolution. IL-10R2 residues required for binding were identified by alanine scanning and used to derive computational models of IL-10/IL-10R1/IL-10R2 and IL-22/IL-22R1/IL-10R2 ternary complexes. The models reveal a conserved binding epitope that is surrounded by two clefts that accommodate the structural and chemical diversity of the cytokines. These results provide a structural framework for interpreting IL-10R2 single nucleotide polymorphisms associated with human disease.

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
• Sponsoring Organization: USDOE
• OSTI ID: 1002452
• Journal Information: Structure, Vol. 18, Issue (5) ; 05, 2010
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

36 MATERIALS SCIENCE
ALANINES
CHAINS
CRYSTAL STRUCTURE
LYMPHOKINES
NUCLEOTIDES
RESIDUES
RESOLUTION