IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v524y2015i7564d10.1038_nature14663.html
   My bibliography  Save this article

Universal allosteric mechanism for Gα activation by GPCRs

Author

Listed:
  • Tilman Flock

    (MRC Laboratory of Molecular Biology)

  • Charles N. J. Ravarani

    (MRC Laboratory of Molecular Biology)

  • Dawei Sun

    (Laboratory of Biomolecular Research, Paul Scherrer Institut
    ETH Zurich)

  • A. J. Venkatakrishnan

    (MRC Laboratory of Molecular Biology
    † Present address: Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA)

  • Melis Kayikci

    (MRC Laboratory of Molecular Biology)

  • Christopher G. Tate

    (MRC Laboratory of Molecular Biology)

  • Dmitry B. Veprintsev

    (Laboratory of Biomolecular Research, Paul Scherrer Institut
    ETH Zurich)

  • M. Madan Babu

    (MRC Laboratory of Molecular Biology)

Abstract

G protein-coupled receptors (GPCRs) allosterically activate heterotrimeric G proteins and trigger GDP release. Given that there are ∼800 human GPCRs and 16 different Gα genes, this raises the question of whether a universal allosteric mechanism governs Gα activation. Here we show that different GPCRs interact with and activate Gα proteins through a highly conserved mechanism. Comparison of Gα with the small G protein Ras reveals how the evolution of short segments that undergo disorder-to-order transitions can decouple regions important for allosteric activation from receptor binding specificity. This might explain how the GPCR–Gα system diversified rapidly, while conserving the allosteric activation mechanism.

Suggested Citation

  • Tilman Flock & Charles N. J. Ravarani & Dawei Sun & A. J. Venkatakrishnan & Melis Kayikci & Christopher G. Tate & Dmitry B. Veprintsev & M. Madan Babu, 2015. "Universal allosteric mechanism for Gα activation by GPCRs," Nature, Nature, vol. 524(7564), pages 173-179, August.
    • Handle: RePEc:nat:nature:v:524:y:2015:i:7564:d:10.1038_nature14663
    DOI: 10.1038/nature14663
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature14663
    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/nature14663?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. Yosuke Toyoda & Angqi Zhu & Fang Kong & Sisi Shan & Jiawei Zhao & Nan Wang & Xiaoou Sun & Linqi Zhang & Chuangye Yan & Brian K. Kobilka & Xiangyu Liu, 2023. "Structural basis of α1A-adrenergic receptor activation and recognition by an extracellular nanobody," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Jie Yin & Yanyong Kang & Aaron P. McGrath & Karen Chapman & Megan Sjodt & Eiji Kimura & Atsutoshi Okabe & Tatsuki Koike & Yuhei Miyanohana & Yuji Shimizu & Rameshu Rallabandi & Peng Lian & Xiaochen Ba, 2022. "Molecular mechanism of the wake-promoting agent TAK-925," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Hiroaki Akasaka & Tatsuki Tanaka & Fumiya K. Sano & Yuma Matsuzaki & Wataru Shihoya & Osamu Nureki, 2022. "Structure of the active Gi-coupled human lysophosphatidic acid receptor 1 complexed with a potent agonist," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    4. Xiuqing Lv & Kaixuan Gao & Jia Nie & Xin Zhang & Shuhao Zhang & Yinhang Ren & Xiaoou Sun & Qi Li & Jingrui Huang & Lijuan Liu & Xiaowen Zhang & Weishe Zhang & Xiangyu Liu, 2023. "Structures of human prostaglandin F2α receptor reveal the mechanism of ligand and G protein selectivity," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    5. Chongzhao You & Yumu Zhang & Peiyu Xu & Sijie Huang & Wanchao Yin & H. Eric Xu & Yi Jiang, 2022. "Structural insights into the peptide selectivity and activation of human neuromedin U receptors," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    6. Manbir Sandhu & Aaron Cho & Ning Ma & Elizaveta Mukhaleva & Yoon Namkung & Sangbae Lee & Soumadwip Ghosh & John H. Lee & David E. Gloriam & Stéphane A. Laporte & M. Madan Babu & Nagarajan Vaidehi, 2022. "Dynamic spatiotemporal determinants modulate GPCR:G protein coupling selectivity and promiscuity," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    7. Yan Chen & Qingtong Zhou & Jiang Wang & Youwei Xu & Yun Wang & Jiahui Yan & Yibing Wang & Qi Zhu & Fenghui Zhao & Chenghao Li & Chuan-Wei Chen & Xiaoqing Cai & Ross A .D. Bathgate & Chun Shen & H. Eri, 2023. "Ligand recognition mechanism of the human relaxin family peptide receptor 4 (RXFP4)," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    8. Jinkang Shen & Dongqi Zhang & Yao Fu & Anqi Chen & Xiaoli Yang & Haitao Zhang, 2022. "Cryo-EM structures of human bradykinin receptor-Gq proteins complexes," Nature Communications, Nature, vol. 13(1), pages 1-10, 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:524:y:2015:i:7564:d:10.1038_nature14663. 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.