| Literature DB >> 14528293 |
Zenichiro Kato1, JunGoo Jee, Hiroaki Shikano, Masaki Mishima, Izuru Ohki, Hidenori Ohnishi, Ailian Li, Kazuyuki Hashimoto, Eiji Matsukuma, Kentaro Omoya, Yutaka Yamamoto, Teruyo Yoneda, Takane Hara, Naomi Kondo, Masahiro Shirakawa.
Abstract
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.Entities:
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Year: 2003 PMID： 14528293 DOI： 10.1038/nsb993
Source DB: PubMed Journal: Nat Struct Biol ISSN： 1072-8368