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Crystal structures of the human adiponectin receptors

Author

Listed:
  • Hiroaki Tanabe

    (RIKEN Systems and Structural Biology Center
    Graduate School of Science, The University of Tokyo
    RIKEN Center for Life Science Technologies
    RIKEN Structural Biology Laboratory)

  • Yoshifumi Fujii

    (RIKEN Systems and Structural Biology Center
    RIKEN Structural Biology Laboratory)

  • Miki Okada-Iwabu

    (Graduate School of Medicine, The University of Tokyo
    22nd Century Medical and Research Center, The University of Tokyo)

  • Masato Iwabu

    (Graduate School of Medicine, The University of Tokyo
    22nd Century Medical and Research Center, The University of Tokyo
    PRESTO, Japan Science and Technology Agency)

  • Yoshihiro Nakamura

    (RIKEN Systems and Structural Biology Center
    RIKEN Center for Life Science Technologies
    RIKEN Structural Biology Laboratory)

  • Toshiaki Hosaka

    (RIKEN Systems and Structural Biology Center
    RIKEN Center for Life Science Technologies)

  • Kanna Motoyama

    (RIKEN Systems and Structural Biology Center)

  • Mariko Ikeda

    (RIKEN Systems and Structural Biology Center
    RIKEN Center for Life Science Technologies)

  • Motoaki Wakiyama

    (RIKEN Systems and Structural Biology Center
    RIKEN Center for Life Science Technologies)

  • Takaho Terada

    (RIKEN Systems and Structural Biology Center
    RIKEN Structural Biology Laboratory)

  • Noboru Ohsawa

    (RIKEN Systems and Structural Biology Center
    RIKEN Center for Life Science Technologies)

  • Masakatsu Hato

    (RIKEN Systems and Structural Biology Center
    RIKEN Center for Life Science Technologies)

  • Satoshi Ogasawara

    (Graduate School of Medicine, Kyoto University)

  • Tomoya Hino

    (Graduate School of Medicine, Kyoto University
    JST, Research Acceleration Program, Membrane Protein Crystallography Project)

  • Takeshi Murata

    (RIKEN Systems and Structural Biology Center
    Graduate School of Medicine, Kyoto University
    JST, Research Acceleration Program, Membrane Protein Crystallography Project
    Graduate School of Science, Chiba University)

  • So Iwata

    (RIKEN Systems and Structural Biology Center
    Graduate School of Medicine, Kyoto University
    JST, Research Acceleration Program, Membrane Protein Crystallography Project
    Membrane Protein Crystallography Group, Imperial College)

  • Kunio Hirata

    (RIKEN SPring-8 Center, Harima Institute)

  • Yoshiaki Kawano

    (RIKEN SPring-8 Center, Harima Institute)

  • Masaki Yamamoto

    (RIKEN SPring-8 Center, Harima Institute)

  • Tomomi Kimura-Someya

    (RIKEN Systems and Structural Biology Center
    RIKEN Center for Life Science Technologies)

  • Mikako Shirouzu

    (RIKEN Systems and Structural Biology Center
    RIKEN Center for Life Science Technologies)

  • Toshimasa Yamauchi

    (Graduate School of Medicine, The University of Tokyo
    22nd Century Medical and Research Center, The University of Tokyo
    CREST, Japan Science and Technology Agency)

  • Takashi Kadowaki

    (Graduate School of Medicine, The University of Tokyo
    22nd Century Medical and Research Center, The University of Tokyo)

  • Shigeyuki Yokoyama

    (RIKEN Systems and Structural Biology Center
    Graduate School of Science, The University of Tokyo
    RIKEN Structural Biology Laboratory)

Abstract

Adiponectin stimulation of its receptors, AdipoR1 and AdipoR2, increases the activities of 5′ AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor (PPAR), respectively, thereby contributing to healthy longevity as key anti-diabetic molecules. AdipoR1 and AdipoR2 were predicted to contain seven transmembrane helices with the opposite topology to G-protein-coupled receptors. Here we report the crystal structures of human AdipoR1 and AdipoR2 at 2.9 and 2.4 Å resolution, respectively, which represent a novel class of receptor structure. The seven-transmembrane helices, conformationally distinct from those of G-protein-coupled receptors, enclose a large cavity where three conserved histidine residues coordinate a zinc ion. The zinc-binding structure may have a role in the adiponectin-stimulated AMPK phosphorylation and UCP2 upregulation. Adiponectin may broadly interact with the extracellular face, rather than the carboxy-terminal tail, of the receptors. The present information will facilitate the understanding of novel structure–function relationships and the development and optimization of AdipoR agonists for the treatment of obesity-related diseases, such as type 2 diabetes.

Suggested Citation

  • Hiroaki Tanabe & Yoshifumi Fujii & Miki Okada-Iwabu & Masato Iwabu & Yoshihiro Nakamura & Toshiaki Hosaka & Kanna Motoyama & Mariko Ikeda & Motoaki Wakiyama & Takaho Terada & Noboru Ohsawa & Masakatsu, 2015. "Crystal structures of the human adiponectin receptors," Nature, Nature, vol. 520(7547), pages 312-316, April.
  • Handle: RePEc:nat:nature:v:520:y:2015:i:7547:d:10.1038_nature14301
    DOI: 10.1038/nature14301
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    Citations

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    Cited by:

    1. Mario Ruiz & Ranjan Devkota & Dimitra Panagaki & Per-Olof Bergh & Delaney Kaper & Marcus Henricsson & Ali Nik & Kasparas Petkevicius & Johanna L. Höög & Mohammad Bohlooly-Y & Peter Carlsson & Jan Boré, 2022. "Sphingosine 1-phosphate mediates adiponectin receptor signaling essential for lipid homeostasis and embryogenesis," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Dandan Qian & Ye Cong & Runhao Wang & Quan Chen & Chuangye Yan & Deshun Gong, 2023. "Structural insight into the human SID1 transmembrane family member 2 reveals its lipid hydrolytic activity," Nature Communications, Nature, vol. 14(1), pages 1-10, December.

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