title: Structure and mechanism of receptor sharing by the IL-10R2 common chain.
abstract: 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 A 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.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Sung-Il
authors.initials: SI
authors.lastname: Yoon
authors.forename: Brandi C
authors.initials: BC
authors.lastname: Jones
authors.forename: Naomi J
authors.initials: NJ
authors.lastname: Logsdon
authors.forename: Bethany D
authors.initials: BD
authors.lastname: Harris
authors.forename: Ashlesha
authors.initials: A
authors.lastname: Deshpande
authors.forename: Svetlana
authors.initials: S
authors.lastname: Radaeva
authors.forename: Brian A
authors.initials: BA
authors.lastname: Halloran
authors.forename: Bin
authors.initials: B
authors.lastname: Gao
authors.forename: Mark R
authors.initials: MR
authors.lastname: Walter
mesh_terms: D000409:Alanine / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D007378:Interleukins; D011485:Protein Binding / Q000235:genetics; D018123:Receptors, Interleukin; D000097043:Interleukin-22
chemical_list: D000409:Alanine; D016207:Cytokines; D016753:Interleukin-10; D007378:Interleukins; D018123:Receptors, Interleukin; D000097043:Interleukin-22; C415369:interleukin-22 receptor
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