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PMID: 20462497 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Structure and mechanism of receptor sharing by the IL-10R2 common chain.

Structure (London, England : 1993) ·Vol. 18 ·No. 5 ·2010-05-12 ·Pages 638-48

Yoon SI, Jones BC, Logsdon NJ, Harris BD, Deshpande A, Radaeva S, Halloran BA, Gao B, Walter MR

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.

MeSH Terms
Alanine/genetics,metabolism Cytokines/chemistry,genetics,metabolism Humans Interleukin-10/chemistry,genetics,metabolism Interleukins Protein Binding/genetics Receptors, Interleukin
Chemicals
Cytokines Interleukins Receptors, Interleukin interleukin-22 receptor Interleukin-10 Alanine interleukin-22
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Yoon Sung-Il
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Jones Brandi C
Logsdon Naomi J
Harris Bethany D
Deshpande Ashlesha
Radaeva Svetlana
Halloran Brian A
Gao Bin
Walter Mark R
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Article Info
Journal
Structure (London, England : 1993)
Abbr.
Structure
ISSN
1878-4186
DOI
10.1016/j.str.2010.02.009
Published
2010-05-12
Pages
638-48
Language
English
Region
United States
NLM ID
101087697
PMCID
PMC2879597
Subset
IM
Grants
NIAID NIH HHS · AI043700 · United States
NIAID NIH HHS · R01 AI047300 · United States
NIAID NIH HHS · R01 AI047300-10 · United States
NIAID NIH HHS · AI043700-08S1 · United States
NIAID NIH HHS · R01 AI047300-08S1 · United States
Corrections
CommentIn
PMID: 20462488
External Links
PubMed source DOI: 10.1016/j.str.2010.02.009 PMC Full Text View journal details
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