IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-14943-4.html
   My bibliography  Save this article

Structure of the G protein chaperone and guanine nucleotide exchange factor Ric-8A bound to Gαi1

Author

Listed:
  • Levi J. McClelland

    (University of Montana)

  • Kaiming Zhang

    (Stanford University)

  • Tung-Chung Mou

    (University of Montana
    University of Montana)

  • Jake Johnston

    (University of Montana
    University of Montana)

  • Cindee Yates-Hansen

    (University of Montana)

  • Shanshan Li

    (Stanford University)

  • Celestine J. Thomas

    (University of Montana
    Regeneron Pharmaceutical, Inc.)

  • Tzanko I. Doukov

    (Stanford University)

  • Sarah Triest

    (Vrije Universiteit Brussel (VUB)
    VIB-VUB Center for Structural Biology, VIB)

  • Alexandre Wohlkonig

    (Vrije Universiteit Brussel (VUB)
    VIB-VUB Center for Structural Biology, VIB)

  • Gregory G. Tall

    (University of Michigan Medical School)

  • Jan Steyaert

    (Vrije Universiteit Brussel (VUB)
    VIB-VUB Center for Structural Biology, VIB)

  • Wah Chiu

    (Stanford University
    Stanford University)

  • Stephen R. Sprang

    (University of Montana
    University of Montana
    University of Montana)

Abstract

Ric-8A is a cytosolic Guanine Nucleotide exchange Factor (GEF) that activates heterotrimeric G protein alpha subunits (Gα) and serves as an essential Gα chaperone. Mechanisms by which Ric-8A catalyzes these activities, which are stimulated by Casein Kinase II phosphorylation, are unknown. We report the structure of the nanobody-stabilized complex of nucleotide-free Gα bound to phosphorylated Ric-8A at near atomic resolution by cryo-electron microscopy and X-ray crystallography. The mechanism of Ric-8A GEF activity differs considerably from that employed by G protein-coupled receptors at the plasma membrane. Ric-8A engages a specific conformation of Gα at multiple interfaces to form a complex that is stabilized by phosphorylation within a Ric-8A segment that connects two Gα binding sites. The C-terminus of Gα is ejected from its beta sheet core, thereby dismantling the GDP binding site. Ric-8A binds to the exposed Gα beta sheet and switch II to stabilize the nucleotide-free state of Gα.

Suggested Citation

  • Levi J. McClelland & Kaiming Zhang & Tung-Chung Mou & Jake Johnston & Cindee Yates-Hansen & Shanshan Li & Celestine J. Thomas & Tzanko I. Doukov & Sarah Triest & Alexandre Wohlkonig & Gregory G. Tall , 2020. "Structure of the G protein chaperone and guanine nucleotide exchange factor Ric-8A bound to Gαi1," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14943-4
    DOI: 10.1038/s41467-020-14943-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-14943-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-14943-4?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
    ---><---

    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:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14943-4. 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.