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

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: FEBS Letters; v. 582, n. 20, p. 2985-2992, SEP 3 2008.
• Web of Science Citations: 58

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 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. (AU)

• FAPESP's process: 06/00182-8 - Structural biophysics of nuclear receptors and related proteins
• Grantee: Igor Polikarpov
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 06/01534-5 - Studies of the interactions of thyroid hormone receptors with DNA and the coregulator proteins using X-ray crystallography
• Grantee: Leandra Watanabe
• Support type: Scholarships in Brazil - Post-Doctorate