Crystal structure of a soluble decoy receptor IL-22BP bound to interleukin-22.
Interleukin-22 (IL-22) plays an important role in the regulation of immune and inflammatory responses in mammals. The IL-22 binding protein (IL-22BP), a soluble receptor that specifically binds IL-22, prevents the IL-22/interleukin-22 receptor 1 (IL-22R1)/interleukin-10 receptor 2 (IL-10R2) complex assembly and blocks IL-22 biological activity. Here we present the crystal structure of the IL-22/IL-22BP complex at 2.75 A resolution. The structure reveals IL-22BP residues critical for IL-22 binding, which were confirmed by site-directed mutagenesis and functional studies. Comparison of IL-22/IL-22BP and IL-22/IL-22R1 crystal structures shows that both receptors display an overlapping IL-22 binding surface, which is consistent with the inhibitory role played by IL-22 binding protein.
de Moura
Patricia Ribeiro
PR
Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos 13560-970, SP, Brazil.
Watanabe
Leandra
L
Bleicher
Lucas
L
Colau
Didier
D
Dumoutier
Laure
L
Lemaire
Muriel M
MM
Renauld
Jean-Christophe
JC
Polikarpov
Igor
I
D001665:Binding Sites / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D053710:Interleukin-10 Receptor beta Subunit / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding / Q000502:physiology; D020836:Protein Structure, Quaternary / Q000502:physiology; D018123:Receptors, Interleukin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000097043:Interleukin-22
D053710:Interleukin-10 Receptor beta Subunit; D007378:Interleukins; D018123:Receptors, Interleukin; D000097043:Interleukin-22; C433253:IL22RA2 protein, human; C415369:interleukin-22 receptor