Bleicher Lucas, de Moura Patricia Ribeiro, Watanabe Leandra, Colau Didier, Dumoutier Laure, Renauld Jean-Christophe, Polikarpov Igor
Instituto de Física de São Carlos, Universidade de São Paulo, CEP 13560-970 São Carlos, SP, Brazil.
FEBS Lett. 2008 Sep 3;582(20):2985-92. doi: 10.1016/j.febslet.2008.07.046. Epub 2008 Aug 7.
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.
白细胞介素-22（IL-22）是白细胞介素-10细胞因子家族的成员，参与抗微生物防御、组织损伤保护与修复以及急性期反应。其信号传导机制涉及IL-22与白细胞介素-22受体1（IL-22R1）的顺序结合，以及该二聚体与白细胞介素-10受体2（IL-10R2）胞外结构域的结合。我们报道了IL-22/IL-22R1复合物的1.9埃晶体结构，揭示了IL-22/IL-22R1界面处的关键相互作用残基。通过定点诱变和功能研究证实了关键残基的功能重要性。基于二元复合物的X射线结构，我们讨论了IL-10R2识别IL-22/IL-22R1的分子基础。
