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 1.9 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.

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

FAPESP[06/00182-8]

FAPESP[06/01534-5]

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

FAPESP[06/60860-0]

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

CNPq[154559/2006-7]

CNPq[473875/2003-9]

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

CAPES

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Belgian Federal Service for Scientific, Technical, and Cultural Affairs

Belgian Federal Service for Scientific, Technical, and Cultural Affairs

Actions de Recherche Concertees of the Communaute Francaise de Belgique

Actions de Recherche Concertees of the Communaute Francaise de Belgique