| | Crystal structure of the IL-22/IL-22R1 complex and its implications for the IL-22 signaling mechanismEdited by Hans Eklund Received 13 June 2008; received in revised form 2 July 2008; accepted 6 July 2008. published online 01 August 2008. Abstract 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 Å 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. Structured summaryIl22 (uniprotkb:Q9GZX6) and IL22R1 (uniprotkb:Q8N6P7) bind (MI:0407) by X-ray crystallography (MI:0114) Abbreviations: IL-22R1, interleukin-22 receptor 1, IL-22, interleukin-22, IL-10, interleukin-10, IL-10R2, interleukin-10 receptor 2, CRF2-9, cytokine receptor family class 2 member 9, CRF2-4, the second chain of the IL-10 receptor complex, IL-20, interleukin-20, IL-24, interleukin-24, IL-10R1, interleukin-10 receptor 1, FBN-III, fibronectin-III domain, IL-4, interleukin-4, IL-4Rα/γc, IL-4 receptor α common γ chain (γc), IL-13Rα1, interleukin-13 receptor α, STAT3, signal transducer and activator of transcription 3, HEK-293, human embryonic kidney 293 cells a Instituto de Física de São Carlos, Universidade de São Paulo, Av. Trabalhador São-Carlense, 400, CEP 13560-970 São Carlos, SP, Brazil b Ludwig Institute for Cancer Research, Brussels Branch, Belgium c Experimental Medicine Unit, Christian de Duve Institute, Université Catholique de Louvain, Brussels, Belgium  Corresponding author. Fax: +55 16 33739881.
PII: S0014-5793(08)00647-9 doi:10.1016/j.febslet.2008.07.046 © 2008 Federation of European Biochemical Societies | |
|
|
ABSTRACT
