The structural basis for receptor recognition of human interleukin-18

  • Nat Commun. 2014 Dec 15;5:5340. doi: 10.1038/ncomms6340.
Naotaka Tsutsumi  1 ,  Takeshi Kimura  2 ,  Kyohei Arita  3 ,  Mariko Ariyoshi  4 ,  Hidenori Ohnishi  2 ,  Takahiro Yamamoto  2 ,  Xiaobing Zuo  5 ,  Katsumi Maenaka  6 ,  Enoch Y Park  7 ,  Naomi Kondo  8 ,  Masahiro Shirakawa  9 ,  Hidehito Tochio  10 ,  Zenichiro Kato  11
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.
PMID: 25500532 DOI: 10.1038/ncomms6340
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.

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