title: 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 1.9A 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.
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, CEP 13560-970 São Carlos, SP, Brazil.
authors.forename: Lucas
authors.initials: L
authors.lastname: Bleicher
authors.forename: Patricia Ribeiro
authors.initials: PR
authors.lastname: de Moura
authors.forename: Leandra
authors.initials: L
authors.lastname: Watanabe
authors.forename: Didier
authors.initials: D
authors.lastname: Colau
authors.forename: Laure
authors.initials: L
authors.lastname: Dumoutier
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Renauld
authors.forename: Igor
authors.initials: I
authors.lastname: Polikarpov
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D018360:Crystallography, X-Ray; D006801:Humans; D007378:Interleukins / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D018123:Receptors, Interleukin / Q000737:chemistry* / Q000235:genetics; D053701:Receptors, Interleukin-10 / Q000737:chemistry; D015398:Signal Transduction; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D000097043:Interleukin-22; C415369:interleukin-22 receptor