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G-protein-coupled receptor inactivation by an allosteric inverse-agonist antibody

Author

Listed:
  • Tomoya Hino

    (Iwata Human Receptor Crystallography Project, ERATO, Japan Science and Technology Agency, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
    Graduate School of Medicine, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
    Present address: Department of Biotechnology, Graduate School of Engineering, Tottori University, 4-101, Koyama-cho minami, Tottori, 680-8552, Japan.)

  • Takatoshi Arakawa

    (Iwata Human Receptor Crystallography Project, ERATO, Japan Science and Technology Agency, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
    Graduate School of Medicine, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan)

  • Hiroko Iwanari

    (Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan)

  • Takami Yurugi-Kobayashi

    (Iwata Human Receptor Crystallography Project, ERATO, Japan Science and Technology Agency, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
    Graduate School of Medicine, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan)

  • Chiyo Ikeda-Suno

    (Iwata Human Receptor Crystallography Project, ERATO, Japan Science and Technology Agency, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
    Graduate School of Medicine, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan)

  • Yoshiko Nakada-Nakura

    (Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan
    Perseus Proteomics Inc, 4-7-6 Komaba, Meguro, Tokyo 153-0041, Japan)

  • Osamu Kusano-Arai

    (Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan
    Institute of Immunology Co. Ltd, 1-1-10 Koraku, Bunkyo, Tokyo 112-0004, Japan)

  • Simone Weyand

    (Iwata Human Receptor Crystallography Project, ERATO, Japan Science and Technology Agency, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
    Membrane Protein Crystallography Group, Imperial College London, Exhibition Road, London SW7 2AZ, UK
    Membrane Protein Laboratory, Diamond Light Source, Harwell Science and Innovation Campus, Chilton, Didcot OX11 0DE, UK
    Research Complex at Harwell, Rutherford Appleton Laboratory, Harwell Oxford, Didcot OX11 0FA, UK)

  • Tatsuro Shimamura

    (Iwata Human Receptor Crystallography Project, ERATO, Japan Science and Technology Agency, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
    Graduate School of Medicine, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan)

  • Norimichi Nomura

    (Iwata Human Receptor Crystallography Project, ERATO, Japan Science and Technology Agency, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
    Graduate School of Medicine, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan)

  • Alexander D. Cameron

    (Iwata Human Receptor Crystallography Project, ERATO, Japan Science and Technology Agency, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
    Membrane Protein Crystallography Group, Imperial College London, Exhibition Road, London SW7 2AZ, UK
    Membrane Protein Laboratory, Diamond Light Source, Harwell Science and Innovation Campus, Chilton, Didcot OX11 0DE, UK
    Research Complex at Harwell, Rutherford Appleton Laboratory, Harwell Oxford, Didcot OX11 0FA, UK)

  • Takuya Kobayashi

    (Iwata Human Receptor Crystallography Project, ERATO, Japan Science and Technology Agency, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
    Graduate School of Medicine, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
    Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Kyoto University Faculty of Medicine, Kyoto 606-8501, Japan)

  • Takao Hamakubo

    (Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan)

  • So Iwata

    (Iwata Human Receptor Crystallography Project, ERATO, Japan Science and Technology Agency, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
    Graduate School of Medicine, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
    Membrane Protein Crystallography Group, Imperial College London, Exhibition Road, London SW7 2AZ, UK
    Membrane Protein Laboratory, Diamond Light Source, Harwell Science and Innovation Campus, Chilton, Didcot OX11 0DE, UK)

  • Takeshi Murata

    (Iwata Human Receptor Crystallography Project, ERATO, Japan Science and Technology Agency, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
    Graduate School of Medicine, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
    Systems and Structural Biology Center, RIKEN, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan
    Graduate School of Science, Chiba University, 1-33 Yayoi-cho, Inage, Chiba 263-8522, Japan)

Abstract

Determination of the crystal structure of the human A2A adenosine receptor in complex with an inverse-agonist antibody shows that the allosteric site of the receptor inhibits agonist binding and that the antibody locks the receptor in an inactive conformation.

Suggested Citation

  • Tomoya Hino & Takatoshi Arakawa & Hiroko Iwanari & Takami Yurugi-Kobayashi & Chiyo Ikeda-Suno & Yoshiko Nakada-Nakura & Osamu Kusano-Arai & Simone Weyand & Tatsuro Shimamura & Norimichi Nomura & Alexa, 2012. "G-protein-coupled receptor inactivation by an allosteric inverse-agonist antibody," Nature, Nature, vol. 482(7384), pages 237-240, February.
    • Handle: RePEc:nat:nature:v:482:y:2012:i:7384:d:10.1038_nature10750
    DOI: 10.1038/nature10750
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    Cited by:

    1. Yongchan Lee & Chunhuan Jin & Ryuichi Ohgaki & Minhui Xu & Satoshi Ogasawara & Rangana Warshamanage & Keitaro Yamashita & Garib Murshudov & Osamu Nureki & Takeshi Murata & Yoshikatsu Kanai, 2025. "Structural basis of anticancer drug recognition and amino acid transport by LAT1," Nature Communications, Nature, vol. 16(1), pages 1-12, December.

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