Crystal structure of the IL-22/IL-22R1 complex and its implications for the IL-22 signaling mechanism.
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.
Bleicher
Lucas
L
Instituto de Física de São Carlos, Universidade de São Paulo, CEP 13560-970 São Carlos, SP, Brazil.
de Moura
Patricia Ribeiro
PR
Watanabe
Leandra
L
Colau
Didier
D
Dumoutier
Laure
L
Renauld
Jean-Christophe
JC
Polikarpov
Igor
I
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
D007378:Interleukins; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D000097043:Interleukin-22; C415369:interleukin-22 receptor