Wang Xinquan, Rickert Mathias, Garcia K Christopher
Howard Hughes Medical Institute, Department of Microbiology and Immunology, Stanford University School of Medicine, 299 Campus Drive, Fairchild D319, Stanford, CA 94305, USA.
Science. 2005 Nov 18;310(5751):1159-63. doi: 10.1126/science.1117893.
Interleukin-2 (IL-2) is an immunoregulatory cytokine that acts through a quaternary receptor signaling complex containing alpha (IL-2Ralpha), beta (IL-2Rbeta), and common gamma chain (gc) receptors. In the structure of the quaternary ectodomain complex as visualized at a resolution of 2.3 angstroms, the binding of IL-2Ralpha to IL-2 stabilizes a secondary binding site for presentation to IL-2Rbeta. gammac is then recruited to the composite surface formed by the IL-2/IL-2Rbeta complex. Consistent with its role as a shared receptor for IL-4, IL-7, IL-9, IL-15, and IL-21, gammac forms degenerate contacts with IL-2. The structure of gammac provides a rationale for loss-of-function mutations found in patients with X-linked severe combined immunodeficiency diseases (X-SCID). This complex structure provides a framework for other gammac-dependent cytokine-receptor interactions and for the engineering of improved IL-2 therapeutics.
白细胞介素-2（IL-2）是一种免疫调节细胞因子，它通过包含α（IL-2Rα）、β（IL-2Rβ）和共同γ链（γc）受体的四聚体受体信号复合物发挥作用。在以2.3埃分辨率可视化的四聚体外结构域复合物结构中，IL-2Rα与IL-2的结合稳定了一个二级结合位点，用于呈递给IL-2Rβ。然后γc被招募到由IL-2/IL-2Rβ复合物形成的复合表面。与其作为IL-4、IL-7、IL-9、IL-15和IL-21的共享受体的作用一致，γc与IL-2形成简并接触。γc的结构为X连锁重症联合免疫缺陷病（X-SCID）患者中发现的功能丧失突变提供了理论依据。这种复杂结构为其他γc依赖性细胞因子-受体相互作用以及改进的IL-2治疗方法的设计提供了框架。
