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Publication Abstract from PubMed

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.

The structure and binding mode of interleukin-18.,Kato Z, Jee J, Shikano H, Mishima M, Ohki I, Ohnishi H, Li A, Hashimoto K, Matsukuma E, Omoya K, Yamamoto Y, Yoneda T, Hara T, Kondo N, Shirakawa M Nat Struct Biol. 2003 Nov;10(11):966-71. Epub 2003 Oct 5. PMID:14528293^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.