We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
The structure and binding mode of interleukin-18.
- Authors
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
- 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.
- Publication
Nature structural biology, 2003, Vol 10, Issue 11, p966
- ISSN
1072-8368
- Publication type
Journal Article
- DOI
10.1038/nsb993