The structure and binding mode of interleukin-18
The structure and binding mode of interleukin-18
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DOI：
10.1038/nsb993
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发表时间：
2003-11-01
期刊：
影响因子：
--
通讯作者：
Shirakawa, M
中科院分区：
文献类型：
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作者：
Kato, Z;Jee, J;Shirakawa, M
白介素-18 (IL-18) 是一种细胞因子，以前称为干扰素-γ- (IFN-γ-) 诱导因子，具有多效性免疫调节功能，包括增强 IFN-γ 的产生、Fas 介导的细胞毒性和 I 型 T 淋巴细胞辅助细胞的发育调节。我们确定了 IL-18 的溶液结构，作为了解其受体激活机制的第一步。它折叠成类似于 IL-1 的 β-三叶形结构。广泛的诱变揭示了三个对受体激活很重要的位点的存在：两个作为IL-18受体α（IL-18Rα）的结合位点，其位置类似于IL-1对I型IL-1受体（IL-1RI）的结合位点，而第三个位点可能参与IL-18受体β（IL-18Rβ）的结合。结构和诱变数据为理解 IL-18 诱导的受体亚基异二聚化提供了基础，这对于受体激活是必需的。
Interleukin-18 (IL-18), a cytokine formerly known as interferon-gamma- (IFN-gamma-) inducing factor, has pleiotropic immunoregulatory functions, including augmentation of IFN-gamma production, Fas-mediated cytotoxicity and developmental regulation of T-lymphocyte helper type I. We determined the solution structure of IL-18 as a first step toward understanding its receptor activation mechanism. It folds into a beta-trefoil structure that resembles that of IL-1. Extensive mutagenesis revealed the presence of three sites that are important for receptor activation: two serve as binding sites for IL-18 receptor alpha (IL-18Ralpha), located at positions similar to those of IL-1 for IL-1 receptor type I (IL-1RI), whereas the third site may be involved in IL-18 receptor beta (IL-18Rbeta) binding. The structure and mutagenesis data provide a basis for understanding the IL-18-induced heterodimerization of receptor subunits, which is necessary for receptor activation.