IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v558y2018i7711d10.1038_s41586-018-0215-y.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-018-0215-y
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/s41586-018-0215-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    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. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:558:y:2018:i:7711:d:10.1038_s41586-018-0215-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.