IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-15864-y.html
   My bibliography  Save this article

A high-resolution description of β1-adrenergic receptor functional dynamics and allosteric coupling from backbone NMR

Author

Listed:
  • Anne Grahl

    (University of Basel)

  • Layara Akemi Abiko

    (University of Basel)

  • Shin Isogai

    (University of Basel)

  • Timothy Sharpe

    (University of Basel)

  • Stephan Grzesiek

    (University of Basel)

Abstract

Signal transmission and regulation of G-protein-coupled receptors (GPCRs) by extra- and intracellular ligands occurs via modulation of complex conformational equilibria, but their exact kinetic details and underlying atomic mechanisms are unknown. Here we quantified these dynamic equilibria in the β1-adrenergic receptor in its apo form and seven ligand complexes using 1H/15N NMR spectroscopy. We observe three major exchanging conformations: an inactive conformation (Ci), a preactive conformation (Cp) and an active conformation (Ca), which becomes fully populated in a ternary complex with a G protein mimicking nanobody. The Ci ↔ Cp exchange occurs on the microsecond scale, the Cp ↔ Ca exchange is slower than ~5 ms and only occurs in the presence of two highly conserved tyrosines (Y5.58, Y7.53), which stabilize the active conformation of TM6. The Cp→Ca chemical shift changes indicate a pivoting motion of the entire TM6 that couples the effector site to the orthosteric ligand pocket.

Suggested Citation

  • Anne Grahl & Layara Akemi Abiko & Shin Isogai & Timothy Sharpe & Stephan Grzesiek, 2020. "A high-resolution description of β1-adrenergic receptor functional dynamics and allosteric coupling from backbone NMR," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15864-y
    DOI: 10.1038/s41467-020-15864-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-15864-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-020-15864-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
    ---><---

    Citations

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


    Cited by:

    1. 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.
    2. Minfei Su & Navid Paknejad & Lan Zhu & Jinan Wang & Hung Nguyen Do & Yinglong Miao & Wei Liu & Richard K. Hite & Xin-Yun Huang, 2022. "Structures of β1-adrenergic receptor in complex with Gs and ligands of different efficacies," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Kazem Asadollahi & Sunnia Rajput & Lazarus Andrew Zhang & Ching-Seng Ang & Shuai Nie & Nicholas A. Williamson & Michael D. W. Griffin & Ross A. D. Bathgate & Daniel J. Scott & Thomas R. Weikl & Guy N., 2023. "Unravelling the mechanism of neurotensin recognition by neurotensin receptor 1," Nature Communications, Nature, vol. 14(1), pages 1-13, 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:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15864-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.