The structure and binding mode of interleukin-18

Zenichiro Kato; Jun Goo 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

doi:10.1038/nsb993

The structure and binding mode of interleukin-18

Zenichiro Kato, Jun Goo 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

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Abstract

Interleukin-18 (IL-18), a cytokine formerly known as interferon-γ (IFN-γ-) inducing factor, has pleiotropic immunoregulatory functions, including augmentation of IFN-γ, 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 β-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 α (IL-18Rα), 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 β (IL-18Rβ) 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.

Original language	English
Pages (from-to)	966-971
Number of pages	6
Journal	Nature Structural Biology
Volume	10
Issue number	11
DOIs	https://doi.org/10.1038/nsb993
State	Published - Nov 2003

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title = "The structure and binding mode of interleukin-18",

abstract = "Interleukin-18 (IL-18), a cytokine formerly known as interferon-γ (IFN-γ-) inducing factor, has pleiotropic immunoregulatory functions, including augmentation of IFN-γ, 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 β-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 α (IL-18Rα), 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 β (IL-18Rβ) 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.",

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AU - Jee, Jun Goo

AU - Shikano, Hiroaki

AU - Mishima, Masaki

AU - Ohki, Izuru

AU - Ohnishi, Hidenori

AU - Li, Ailian

AU - Hashimoto, Kazuyuki

AU - Matsukuma, Eiji

AU - Omoya, Kentaro

AU - Yamamoto, Yutaka

AU - Yoneda, Teruyo

AU - Hara, Takane

AU - Kondo, Naomi

AU - Shirakawa, Masahiro

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AB - Interleukin-18 (IL-18), a cytokine formerly known as interferon-γ (IFN-γ-) inducing factor, has pleiotropic immunoregulatory functions, including augmentation of IFN-γ, 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 β-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 α (IL-18Rα), 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 β (IL-18Rβ) 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.

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The structure and binding mode of interleukin-18

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