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Cryo-EM structure of human rhodopsin bound to an inhibitory G protein

Author

Listed:
  • Yanyong Kang

    (Van Andel Research Institute)

  • Oleg Kuybeda

    (Frederick National Laboratory for Cancer Research)

  • Parker W. de Waal

    (Van Andel Research Institute)

  • Somnath Mukherjee

    (University of Chicago)

  • Ned Van Eps

    (University of Toronto)

  • Przemyslaw Dutka

    (University of Chicago
    Jagiellonian University)

  • X. Edward Zhou

    (Van Andel Research Institute)

  • Alberto Bartesaghi

    (Frederick National Laboratory for Cancer Research)

  • Satchal Erramilli

    (University of Chicago)

  • Takefumi Morizumi

    (University of Toronto)

  • Xin Gu

    (Van Andel Research Institute)

  • Yanting Yin

    (Van Andel Research Institute)

  • Ping Liu

    (University of Chinese Academy of Sciences
    Chinese Academy of Sciences)

  • Yi Jiang

    (Chinese Academy of Sciences)

  • Xing Meng

    (Van Andel Research Institute)

  • Gongpu Zhao

    (Van Andel Research Institute)

  • Karsten Melcher

    (Van Andel Research Institute)

  • Oliver P. Ernst

    (University of Toronto
    University of Toronto)

  • Anthony A. Kossiakoff

    (University of Chicago
    University of Chicago)

  • Sriram Subramaniam

    (Frederick National Laboratory for Cancer Research
    National Cancer Institute, NIH)

  • H. Eric Xu

    (Van Andel Research Institute
    Chinese Academy of Sciences)

Abstract

G-protein-coupled receptors comprise the largest family of mammalian transmembrane receptors. They mediate numerous cellular pathways by coupling with downstream signalling transducers, including the hetrotrimeric G proteins Gs (stimulatory) and Gi (inhibitory) and several arrestin proteins. The structural mechanisms that define how G-protein-coupled receptors selectively couple to a specific type of G protein or arrestin remain unknown. Here, using cryo-electron microscopy, we show that the major interactions between activated rhodopsin and Gi are mediated by the C-terminal helix of the Gi α-subunit, which is wedged into the cytoplasmic cavity of the transmembrane helix bundle and directly contacts the amino terminus of helix 8 of rhodopsin. Structural comparisons of inactive, Gi-bound and arrestin-bound forms of rhodopsin with inactive and Gs-bound forms of the β2-adrenergic receptor provide a foundation to understand the unique structural signatures that are associated with the recognition of Gs, Gi and arrestin by activated G-protein-coupled receptors.

Suggested Citation

  • Yanyong Kang & Oleg Kuybeda & Parker W. de Waal & Somnath Mukherjee & Ned Van Eps & Przemyslaw Dutka & X. Edward Zhou & Alberto Bartesaghi & Satchal Erramilli & Takefumi Morizumi & Xin Gu & Yanting Yi, 2018. "Cryo-EM structure of human rhodopsin bound to an inhibitory G protein," Nature, Nature, vol. 558(7711), pages 553-558, June.
    • Handle: RePEc:nat:nature:v:558:y:2018:i:7711:d:10.1038_s41586-018-0215-y
    DOI: 10.1038/s41586-018-0215-y
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    Cited by:

    1. Jae-Hyun Park & Kouki Kawakami & Naito Ishimoto & Tatsuya Ikuta & Mio Ohki & Toru Ekimoto & Mitsunori Ikeguchi & Dong-Sun Lee & Young-Ho Lee & Jeremy R. H. Tame & Asuka Inoue & Sam-Yong Park, 2023. "Structural basis for ligand recognition and signaling of hydroxy-carboxylic acid receptor 2," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Geng Chen & Jun Xu & Asuka Inoue & Maximilian F. Schmidt & Chen Bai & Qiuyuan Lu & Peter Gmeiner & Zheng Liu & Yang Du, 2022. "Activation and allosteric regulation of the orphan GPR88-Gi1 signaling complex," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Andrew J. Y. Jones & Thomas H. Harman & Matthew Harris & Oliver E. Lewis & Graham Ladds & Daniel Nietlispach, 2024. "Binding kinetics drive G protein subtype selectivity at the β1-adrenergic receptor," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    4. Yang Yang & Hye Jin Kang & Ruogu Gao & Jingjing Wang & Gye Won Han & Jeffrey F. DiBerto & Lijie Wu & Jiahui Tong & Lu Qu & Yiran Wu & Ryan Pileski & Xuemei Li & Xuejun Cai Zhang & Suwen Zhao & Terry K, 2023. "Structural insights into the human niacin receptor HCA2-Gi signalling complex," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    5. Chaehee Park & Jinuk Kim & Seung-Bum Ko & Yeol Kyo Choi & Hyeongseop Jeong & Hyeonuk Woo & Hyunook Kang & Injin Bang & Sang Ah Kim & Tae-Young Yoon & Chaok Seok & Wonpil Im & Hee-Jung Choi, 2022. "Structural basis of neuropeptide Y signaling through Y1 receptor," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    6. Chulwon Choi & Jungnam Bae & Seonghan Kim & Seho Lee & Hyunook Kang & Jinuk Kim & Injin Bang & Kiheon Kim & Won-Ki Huh & Chaok Seok & Hahnbeom Park & Wonpil Im & Hee-Jung Choi, 2023. "Understanding the molecular mechanisms of odorant binding and activation of the human OR52 family," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    7. Marin Matic & Pasquale Miglionico & Manae Tatsumi & Asuka Inoue & Francesco Raimondi, 2023. "GPCRome-wide analysis of G-protein-coupling diversity using a computational biology approach," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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