title: The structural basis for receptor recognition of human interleukin-18.
abstract: Interleukin (IL)-18 is a proinflammatory cytokine that belongs to the IL-1 family and plays an important role in inflammation. The uncontrolled release of this cytokine is associated with severe chronic inflammatory disease. IL-18 forms a signalling complex with the IL-18 receptor α (Rα) and β (Rβ) chains at the plasma membrane, which induces multiple inflammatory cytokines. Here, we present a crystal structure of human IL-18 bound to the two receptor extracellular domains. Generally, the receptors' recognition mode for IL-18 is similar to IL-1β; however, certain notable differences were observed. The architecture of the IL-18 receptor second domain (D2) is unique among the other IL-1R family members, which presumably distinguishes them from the IL-1 receptors that exhibit a more promiscuous ligand recognition mode. The structures and associated biochemical and cellular data should aid in developing novel drugs to neutralize IL-18 activity.
authors.affiliation: Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan.
authors.forename: Naotaka
authors.initials: N
authors.lastname: Tsutsumi
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Gifu University, Yanagido 1-1, Gifu 501-1194, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Graduate School of Nanobioscience, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama Kanagawa 230-0045, Japan.
authors.forename: Kyohei
authors.initials: K
authors.lastname: Arita
authors.affiliation: 1] Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan [2] Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Ariyoshi
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Gifu University, Yanagido 1-1, Gifu 501-1194, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ohnishi
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Gifu University, Yanagido 1-1, Gifu 501-1194, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: X-Ray Science Division, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, Illinois 60439, USA.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Zuo
authors.affiliation: Laboratory of Biomolecular Science and Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, , Kita-12, Nishi-6, Kita-ki, Sapporo 060-0812, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Maenaka
authors.affiliation: Research Institute of Green Science and Technology, Department of Bioscience, Graduate school of Science and Technology, Shizuoka University, 836 Ohya Suruga-ku, Shizuoka 422-8529, Japan.
authors.forename: Enoch Y
authors.initials: EY
authors.lastname: Park
authors.affiliation: 1] Department of Pediatrics, Graduate School of Medicine, Gifu University, Yanagido 1-1, Gifu 501-1194, Japan [2] Heisei College of Health Sciences, 180 Kurono, Gifu 501-1131, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Kondo
authors.affiliation: 1] Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan [2] Core Research of Evolution Science (CREST), Japan Sciences and Technology Agency, Tokyo 102-0076, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shirakawa
authors.affiliation: Department of Biophysics, Graduate School of Science, Kyoto University, Kitashirakawa-oiwake, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Hidehito
authors.initials: H
authors.lastname: Tochio
authors.affiliation: 1] Department of Pediatrics, Graduate School of Medicine, Gifu University, Yanagido 1-1, Gifu 501-1194, Japan [2] Biomedical Informatics, Medical Information Sciences Division, The United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu 501-1194, Japan.
authors.forename: Zenichiro
authors.initials: Z
authors.lastname: Kato
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D001665:Binding Sites; D018360:Crystallography, X-Ray; D015870:Gene Expression; D006801:Humans; D053577:Interleukin-1 Receptor Accessory Protein / Q000737:chemistry / Q000235:genetics; D020382:Interleukin-18 / Q000737:chemistry* / Q000235:genetics; D053583:Interleukin-1beta / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry* / Q000235:genetics; D018123:Receptors, Interleukin / Q000737:chemistry / Q000235:genetics; D053724:Receptors, Interleukin-18 / Q000737:chemistry* / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D061987:Sf9 Cells; D018411:Spodoptera
chemical_list: C000589760:IL18 protein, human; C507765:IL1RAP protein, human; D053577:Interleukin-1 Receptor Accessory Protein; D020382:Interleukin-18; D053583:Interleukin-1beta; D021122:Protein Subunits; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D011994:Recombinant Proteins; C571244:interleukin-36 receptor, human