Crystal structure of the IL-22/IL-22R1 complex and its implications for the IL-22 signaling mechanism

被引：88

作者：

Bleicher, Lucas ^{[1
]}

de Moura, Patricia Ribeiro ^{[1
]}

Watanabe, Leandra ^{[1
]}

Colau, Didier ^{[2
]}

Dumoutier, Laure ^{[2
,3
]}

Renauld, Jean-Christophe ^{[2
,3
]}

Polikarpov, Igor ^{[1
]}

机构：

[1] Univ Sao Paulo, Inst Fis Sao Carlos, BR-13560970 Sao Carlos, SP, Brazil

[2] Ludwig Inst Canc Res, Brussels Branch, Brussels, Belgium

[3] Univ Catholique Louvain, Christian Duve Inst, Expt Med Unit, B-1200 Brussels, Belgium

来源：

FEBS LETTERS | 2008年 / 582卷 / 20期

基金：

巴西圣保罗研究基金会;

关键词：

cytokines; IL-22R1; IL-22; interleukins; immunology; X-ray crystallography;

D O I：

10.1016/j.febslet.2008.07.046

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Interleukin-22 (IL-22) is a member of the interleukin-10 cytokine family, which is involved in anti-microbial defenses, tissue damage protection and repair, and acute phase responses. Its signaling mechanism involves the sequential binding of IL-22 to interleukin-22 receptor 1 (IL-22R1), and of this dimer to interleukin-10 receptor 2 (IL-10R2) extracellular domain. We report a 1.9 A crystal structure of the IL-22/IL-22R1 complex, revealing crucial interacting residues at the IL-22/IL-22R1 interface. Functional importance of key residues was confirmed by site-directed mutagenesis and functional studies. Based on the X-ray structure of the binary complex, we discuss a molecular basis of the IL-22/IL-22R1 recognition by IL-10R2.

引用

页码：2985 / 2992

页数：8

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