PMID- 14528293 OWN - NLM STAT- MEDLINE DCOM- 20031224 LR - 20220409 IS - 1072-8368 (Print) IS - 1072-8368 (Linking) VI - 10 IP - 11 DP - 2003 Nov TI - The structure and binding mode of interleukin-18. PG - 966-71 AB - 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. FAU - Kato, Zenichiro AU - Kato Z AD - Department of Pediatrics, Gifu University School of Medicine, Tsukasa 40, Gifu 500-8705, Japan. zen-k@cc.gifu-u.ac.jp FAU - Jee, JunGoo AU - Jee J FAU - Shikano, Hiroaki AU - Shikano H FAU - Mishima, Masaki AU - Mishima M FAU - Ohki, Izuru AU - Ohki I FAU - Ohnishi, Hidenori AU - Ohnishi H FAU - Li, Ailian AU - Li A FAU - Hashimoto, Kazuyuki AU - Hashimoto K FAU - Matsukuma, Eiji AU - Matsukuma E FAU - Omoya, Kentaro AU - Omoya K FAU - Yamamoto, Yutaka AU - Yamamoto Y FAU - Yoneda, Teruyo AU - Yoneda T FAU - Hara, Takane AU - Hara T FAU - Kondo, Naomi AU - Kondo N FAU - Shirakawa, Masahiro AU - Shirakawa M LA - eng SI - PDB/1ITB SI - PDB/1JOS SI - PDB/2I1B PT - Journal Article DEP - 20031005 PL - United States TA - Nat Struct Biol JT - Nature structural biology JID - 9421566 RN - 0 (IL18R1 protein, human) RN - 0 (Interleukin-18) RN - 0 (Interleukin-18 Receptor alpha Subunit) RN - 0 (Receptors, Interleukin) RN - 0 (Receptors, Interleukin-18) SB - IM MH - Amino Acid Sequence MH - Binding Sites MH - Humans MH - Interleukin-18/*chemistry/*metabolism MH - Interleukin-18 Receptor alpha Subunit MH - Molecular Sequence Data MH - Receptors, Interleukin/metabolism MH - Receptors, Interleukin-18 EDAT- 2003/10/07 05:00 MHDA- 2003/12/25 05:00 CRDT- 2003/10/07 05:00 PHST- 2002/12/17 00:00 [received] PHST- 2003/08/13 00:00 [accepted] PHST- 2003/10/07 05:00 [pubmed] PHST- 2003/12/25 05:00 [medline] PHST- 2003/10/07 05:00 [entrez] AID - nsb993 [pii] AID - 10.1038/nsb993 [doi] PST - ppublish SO - Nat Struct Biol. 2003 Nov;10(11):966-71. doi: 10.1038/nsb993. Epub 2003 Oct 5.