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

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 1.9Å 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 summary

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/γ_c, 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

Keywords: Cytokines, IL-22R1, IL-22, Interleukins, Immunology, X-ray crystallography