Rickert Mathias, Wang Xinquan, Boulanger Martin J, Goriatcheva Natalia, Garcia K Christopher
Departments of Microbiology and Immunology, and Structural Biology, Stanford University School of Medicine, 299 Campus Drive, Fairchild D319, Stanford, CA 94305-5124, USA.
Science. 2005 Jun 3;308(5727):1477-80. doi: 10.1126/science.1109745.
Interleukin-2 (IL-2) is an immunoregulatory cytokine that binds sequentially to the alpha (IL-2Ralpha), beta (IL-2Rbeta), and common gamma chain (gammac) receptor subunits. Here we present the 2.8 angstrom crystal structure of a complex between human IL-2 and IL-2Ralpha, which interact in a docking mode distinct from that of other cytokine receptor complexes. IL-2Ralpha is composed of strand-swapped "sushi-like" domains, unlike the classical cytokine receptor fold. As a result of this domain swap, IL-2Ralpha uses a composite surface to dock into a groove on IL-2 that also serves as a binding site for antagonist drugs. With this complex, we now have representative structures for each class of hematopoietic cytokine receptor-docking modules.
白细胞介素-2（IL-2）是一种免疫调节细胞因子，它依次与α（IL-2Rα）、β（IL-2Rβ）和共同γ链（γc）受体亚基结合。在此，我们展示了人IL-2与IL-2Rα复合物的2.8埃晶体结构，它们以一种不同于其他细胞因子受体复合物的对接模式相互作用。IL-2Rα由链交换的“寿司样”结构域组成，不同于经典的细胞因子受体折叠结构。由于这种结构域交换，IL-2Rα利用一个复合表面对接至IL-2上的一个凹槽中，该凹槽也是拮抗剂药物的结合位点。有了这个复合物，我们现在拥有了每一类造血细胞因子受体对接模块的代表性结构。
