IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v594y2021i7864d10.1038_s41586-021-03507-1.html
   My bibliography  Save this article

Structural basis of GABAB receptor–Gi protein coupling

Author

Listed:
  • Cangsong Shen

    (Huazhong University of Science and Technology (HUST)
    Zhejiang University School of Medicine
    Zhejiang University Medical Center)

  • Chunyou Mao

    (Zhejiang University School of Medicine
    Zhejiang University Medical Center
    Zhejiang Provincial Key Laboratory of Immunity and Inflammatory Diseases)

  • Chanjuan Xu

    (Huazhong University of Science and Technology (HUST)
    Guangzhou Regenerative Medicine and Health Guangdong Laboratory)

  • Nan Jin

    (Huazhong University of Science and Technology (HUST)
    Zhejiang University School of Medicine
    Zhejiang University Medical Center)

  • Huibing Zhang

    (Zhejiang University School of Medicine
    Zhejiang University Medical Center
    Zhejiang Provincial Key Laboratory of Immunity and Inflammatory Diseases)

  • Dan-Dan Shen

    (Zhejiang University School of Medicine
    Zhejiang University Medical Center
    Zhejiang Provincial Key Laboratory of Immunity and Inflammatory Diseases)

  • Qingya Shen

    (Zhejiang University School of Medicine
    Zhejiang University Medical Center
    Zhejiang Provincial Key Laboratory of Immunity and Inflammatory Diseases)

  • Xiaomei Wang

    (Huazhong University of Science and Technology (HUST))

  • Tingjun Hou

    (Zhejiang University)

  • Zhong Chen

    (Zhejiang Chinese Medical University)

  • Philippe Rondard

    (Université de Montpellier, CNRS, INSERM)

  • Jean-Philippe Pin

    (Université de Montpellier, CNRS, INSERM)

  • Yan Zhang

    (Zhejiang University School of Medicine
    Zhejiang University Medical Center
    Zhejiang Provincial Key Laboratory of Immunity and Inflammatory Diseases
    Zhejiang University School of Medicine)

  • Jianfeng Liu

    (Huazhong University of Science and Technology (HUST)
    Guangzhou Regenerative Medicine and Health Guangdong Laboratory)

Abstract

G-protein-coupled receptors (GPCRs) have central roles in intercellular communication1,2. Structural studies have revealed how GPCRs can activate G proteins. However, whether this mechanism is conserved among all classes of GPCR remains unknown. Here we report the structure of the class-C heterodimeric GABAB receptor, which is activated by the inhibitory transmitter GABA, in its active form complexed with Gi1 protein. We found that a single G protein interacts with the GB2 subunit of the GABAB receptor at a site that mainly involves intracellular loop 2 on the side of the transmembrane domain. This is in contrast to the G protein binding in a central cavity, as has been observed with other classes of GPCR. This binding mode results from the active form of the transmembrane domain of this GABAB receptor being different from that of other GPCRs, as it shows no outside movement of transmembrane helix 6. Our work also provides details of the inter- and intra-subunit changes that link agonist binding to G-protein activation in this heterodimeric complex.

Suggested Citation

  • Cangsong Shen & Chunyou Mao & Chanjuan Xu & Nan Jin & Huibing Zhang & Dan-Dan Shen & Qingya Shen & Xiaomei Wang & Tingjun Hou & Zhong Chen & Philippe Rondard & Jean-Philippe Pin & Yan Zhang & Jianfeng, 2021. "Structural basis of GABAB receptor–Gi protein coupling," Nature, Nature, vol. 594(7864), pages 594-598, June.
    • Handle: RePEc:nat:nature:v:594:y:2021:i:7864:d:10.1038_s41586-021-03507-1
    DOI: 10.1038/s41586-021-03507-1
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-021-03507-1
    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/s41586-021-03507-1?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. Chunyou Mao & Mengru Gao & Shao-Kun Zang & Yanqing Zhu & Dan-Dan Shen & Li-Nan Chen & Liu Yang & Zhiwei Wang & Huibing Zhang & Wei-Wei Wang & Qingya Shen & Yanhui Lu & Xin Ma & Yan Zhang, 2023. "Orthosteric and allosteric modulation of human HCAR2 signaling complex," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    2. Marie-Lise Jobin & Sana Siddig & Zsombor Koszegi & Yann Lanoiselée & Vladimir Khayenko & Titiwat Sungkaworn & Christian Werner & Kerstin Seier & Christin Misigaiski & Giovanna Mantovani & Markus Sauer, 2023. "Filamin A organizes γ‑aminobutyric acid type B receptors at the plasma membrane," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Yaejin Yun & Hyeongseop Jeong & Thibaut Laboute & Kirill A. Martemyanov & Hyung Ho Lee, 2024. "Cryo-EM structure of human class C orphan GPCR GPR179 involved in visual processing," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    4. Junke Liu & Hengmin Tang & Chanjuan Xu & Shengnan Zhou & Xunying Zhu & Yuanyuan Li & Laurent Prézeau & Tao Xu & Jean-Philippe Pin & Philippe Rondard & Wei Ji & Jianfeng Liu, 2022. "Biased signaling due to oligomerization of the G protein-coupled platelet-activating factor receptor," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. Eunyoung Jeong & Yoojoong Kim & Jihong Jeong & Yunje Cho, 2021. "Structure of the class C orphan GPCR GPR158 in complex with RGS7-Gβ5," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    6. Moon Young Yang & Soo-Kyung Kim & William A. Goddard, 2022. "G protein coupling and activation of the metabotropic GABAB heterodimer," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    7. Chanjuan Xu & Yiwei Zhou & Yuxuan Liu & Li Lin & Peng Liu & Xiaomei Wang & Zhengyuan Xu & Jean-Philippe Pin & Philippe Rondard & Jianfeng Liu, 2024. "Specific pharmacological and Gi/o protein responses of some native GPCRs in neurons," Nature Communications, Nature, vol. 15(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:594:y:2021:i:7864:d:10.1038_s41586-021-03507-1. 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.