Kato Zenichiro, Jee JunGoo, Shikano Hiroaki, Mishima Masaki, Ohki Izuru, Ohnishi Hidenori, Li Ailian, Hashimoto Kazuyuki, Matsukuma Eiji, Omoya Kentaro, Yamamoto Yutaka, Yoneda Teruyo, Hara Takane, Kondo Naomi, Shirakawa Masahiro
Department of Pediatrics, Gifu University School of Medicine, Tsukasa 40, Gifu 500-8705, Japan.
Nat Struct Biol. 2003 Nov;10(11):966-71. doi: 10.1038/nsb993. Epub 2003 Oct 5.
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.
白细胞介素-18（IL-18），一种以前被称为γ-干扰素（IFN-γ）诱导因子的细胞因子，具有多效性免疫调节功能，包括增强IFN-γ的产生、Fas介导的细胞毒性以及I型辅助性T淋巴细胞的发育调节。我们确定了IL-18的溶液结构，作为理解其受体激活机制的第一步。它折叠成一个类似于IL-1的β-三叶结构。广泛的诱变揭示了三个对受体激活很重要的位点：两个作为IL-18受体α（IL-18Rα）的结合位点，其位置与IL-1对I型IL-1受体（IL-1RI）的位置相似，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，这是受体激活所必需的。
