title: The structure and binding mode of interleukin-18.
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.
authors.affiliation: Department of Pediatrics, Gifu University School of Medicine, Tsukasa 40, Gifu 500-8705, Japan. zen-k@cc.gifu-u.ac.jp
authors.forename: Zenichiro
authors.initials: Z
authors.lastname: Kato
authors.forename: JunGoo
authors.initials: J
authors.lastname: Jee
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shikano
authors.forename: Masaki
authors.initials: M
authors.lastname: Mishima
authors.forename: Izuru
authors.initials: I
authors.lastname: Ohki
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ohnishi
authors.forename: Ailian
authors.initials: A
authors.lastname: Li
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Eiji
authors.initials: E
authors.lastname: Matsukuma
authors.forename: Kentaro
authors.initials: K
authors.lastname: Omoya
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Teruyo
authors.initials: T
authors.lastname: Yoneda
authors.forename: Takane
authors.initials: T
authors.lastname: Hara
authors.forename: Naomi
authors.initials: N
authors.lastname: Kondo
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shirakawa
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D006801:Humans; D020382:Interleukin-18 / Q000737:chemistry* / Q000378:metabolism*; D053727:Interleukin-18 Receptor alpha Subunit; D008969:Molecular Sequence Data; D018123:Receptors, Interleukin / Q000378:metabolism; D053724:Receptors, Interleukin-18
chemical_list: C508572:IL18R1 protein, human; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18