The structural basis for receptor recognition of human interleukin-18

Naotaka Tsutsumi; Takeshi Kimura; Kyohei Arita; Mariko Ariyoshi; Hidenori Ohnishi; Takahiro Yamamoto; Xiaobing Zuo; Katsumi Maenaka; Enoch Y Park; Naomi Kondo; Masahiro Shirakawa; Hidehito Tochio; Zenichiro Kato

doi:10.1038/ncomms6340

The structural basis for receptor recognition of human interleukin-18

Nat Commun. 2014 Dec 15:5:5340. doi: 10.1038/ncomms6340.

Authors

Affiliations

¹ Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan.
² Department of Pediatrics, Graduate School of Medicine, Gifu University, Yanagido 1-1, Gifu 501-1194, Japan.
³ Graduate School of Nanobioscience, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama Kanagawa 230-0045, Japan.
⁴ 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.
⁵ X-Ray Science Division, Argonne National Laboratory, 9700 South Cass Avenue, Argonne, Illinois 60439, USA.
⁶ 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.
⁷ 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.
⁸ 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.
⁹ 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.
¹⁰ Department of Biophysics, Graduate School of Science, Kyoto University, Kitashirakawa-oiwake, Sakyo-ku, Kyoto 606-8502, Japan.
¹¹ 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.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Baculoviridae / genetics
Binding Sites
Crystallography, X-Ray
Gene Expression
Humans
Interleukin-1 Receptor Accessory Protein / chemistry
Interleukin-1 Receptor Accessory Protein / genetics
Interleukin-18 / chemistry*
Interleukin-18 / genetics
Interleukin-1beta / chemistry*
Interleukin-1beta / genetics
Molecular Sequence Data
Mutation
Protein Binding
Protein Structure, Secondary
Protein Structure, Tertiary
Protein Subunits / chemistry*
Protein Subunits / genetics
Receptors, Interleukin / chemistry
Receptors, Interleukin / genetics
Receptors, Interleukin-18 / chemistry*
Receptors, Interleukin-18 / genetics
Recombinant Proteins / chemistry
Recombinant Proteins / genetics
Sequence Homology, Amino Acid
Sf9 Cells
Spodoptera

Substances

IL18 protein, human
IL1RAP protein, human
Interleukin-1 Receptor Accessory Protein
Interleukin-18
Interleukin-1beta
Protein Subunits
Receptors, Interleukin
Receptors, Interleukin-18
Recombinant Proteins
interleukin-36 receptor, human

Associated data

PDB/3WO2
PDB/3WO3
PDB/3WO4

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding