de Moura Patricia Ribeiro, Watanabe Leandra, Bleicher Lucas, Colau Didier, Dumoutier Laure, Lemaire Muriel M, Renauld Jean-Christophe, Polikarpov Igor
Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos 13560-970, SP, Brazil.
FEBS Lett. 2009 Apr 2;583(7):1072-7. doi: 10.1016/j.febslet.2009.03.006. Epub 2009 Mar 11.
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.
白细胞介素-22（IL-22）在哺乳动物免疫和炎症反应的调节中发挥重要作用。IL-22结合蛋白（IL-22BP）是一种特异性结合IL-22的可溶性受体，可阻止IL-22/白细胞介素-22受体1（IL-22R1）/白细胞介素-10受体2（IL-10R2）复合物的组装，并阻断IL-22的生物学活性。在此，我们展示了分辨率为2.75 Å的IL-22/IL-22BP复合物的晶体结构。该结构揭示了对IL-22结合至关重要的IL-22BP残基，这通过定点诱变和功能研究得到了证实。IL-22/IL-22BP与IL-22/IL-22R1晶体结构的比较表明，两种受体均显示出重叠的IL-22结合表面，这与IL-22结合蛋白所起的抑制作用一致。
