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The structural basis for receptor recognition of human interleukin-18

Author

Listed:
  • Naotaka Tsutsumi

    (Graduate School of Engineering, Kyoto University)

  • Takeshi Kimura

    (Graduate School of Medicine, Gifu University)

  • Kyohei Arita

    (Graduate School of Nanobioscience, Yokohama City University)

  • Mariko Ariyoshi

    (Graduate School of Engineering, Kyoto University
    Institute for Integrated Cell-Material Sciences, Kyoto University)

  • Hidenori Ohnishi

    (Graduate School of Medicine, Gifu University)

  • Takahiro Yamamoto

    (Graduate School of Medicine, Gifu University)

  • Xiaobing Zuo

    (Argonne National Laboratory)

  • Katsumi Maenaka

    (Laboratory of Biomolecular Science and Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University)

  • Enoch Y. Park

    (Research Institute of Green Science and Technology, Graduate school of Science and Technology, Shizuoka University)

  • Naomi Kondo

    (Graduate School of Medicine, Gifu University
    Heisei College of Health Sciences)

  • Masahiro Shirakawa

    (Graduate School of Engineering, Kyoto University
    Core Research of Evolution Science (CREST), Japan Sciences and Technology Agency)

  • Hidehito Tochio

    (Graduate School of Science, Kyoto University, Kitashirakawa-oiwake, Sakyo-ku)

  • Zenichiro Kato

    (Graduate School of Medicine, Gifu University
    Biomedical Informatics, The United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University)

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.

Suggested Citation

  • Naotaka Tsutsumi & Takeshi Kimura & Kyohei Arita & Mariko Ariyoshi & Hidenori Ohnishi & Takahiro Yamamoto & Xiaobing Zuo & Katsumi Maenaka & Enoch Y. Park & Naomi Kondo & Masahiro Shirakawa & Hidehito, 2014. "The structural basis for receptor recognition of human interleukin-18," Nature Communications, Nature, vol. 5(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6340
    DOI: 10.1038/ncomms6340
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