IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v454y2008i7203d10.1038_nature07101.html
   My bibliography  Save this article

Structure of a β1-adrenergic G-protein-coupled receptor

Author

Listed:
  • Tony Warne

    (MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK)

  • Maria J. Serrano-Vega

    (MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK)

  • Jillian G. Baker

    (Institute of Cell Signalling, Medical School, Queen’s Medical Centre, University of Nottingham)

  • Rouslan Moukhametzianov

    (MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK)

  • Patricia C. Edwards

    (MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK)

  • Richard Henderson

    (MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK)

  • Andrew G. W. Leslie

    (MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK)

  • Christopher G. Tate

    (MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK)

  • Gebhard F. X. Schertler

    (MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK)

Abstract

G-protein-coupled receptors have a major role in transmembrane signalling in most eukaryotes and many are important drug targets. Here we report the 2.7 Å resolution crystal structure of a β1-adrenergic receptor in complex with the high-affinity antagonist cyanopindolol. The modified turkey (Meleagris gallopavo) receptor was selected to be in its antagonist conformation and its thermostability improved by earlier limited mutagenesis. The ligand-binding pocket comprises 15 side chains from amino acid residues in 4 transmembrane α-helices and extracellular loop 2. This loop defines the entrance of the ligand-binding pocket and is stabilized by two disulphide bonds and a sodium ion. Binding of cyanopindolol to the β1-adrenergic receptor and binding of carazolol to the β2-adrenergic receptor involve similar interactions. A short well-defined helix in cytoplasmic loop 2, not observed in either rhodopsin or the β2-adrenergic receptor, directly interacts by means of a tyrosine with the highly conserved DRY motif at the end of helix 3 that is essential for receptor activation.

Suggested Citation

  • Tony Warne & Maria J. Serrano-Vega & Jillian G. Baker & Rouslan Moukhametzianov & Patricia C. Edwards & Richard Henderson & Andrew G. W. Leslie & Christopher G. Tate & Gebhard F. X. Schertler, 2008. "Structure of a β1-adrenergic G-protein-coupled receptor," Nature, Nature, vol. 454(7203), pages 486-491, July.
    • Handle: RePEc:nat:nature:v:454:y:2008:i:7203:d:10.1038_nature07101
    DOI: 10.1038/nature07101
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature07101
    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/nature07101?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. Joanna Toporowska & Parth Kapoor & Maria Musgaard & Karolina Gherbi & Kathy Sengmany & Feng Qu & Mark Soave & Hsin-Yung Yen & Kjetil Hansen & Ali Jazayeri & Jonathan T. S. Hopper & Argyris Politis, 2024. "Ligand-induced conformational changes in the β1-adrenergic receptor revealed by hydrogen-deuterium exchange mass spectrometry," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Yun Zhu & Bo-Ji Peng & Smriti Kumar & Lauren Stover & Jing-Yuan Chang & Jixing Lyu & Tianqi Zhang & Samantha Schrecke & Djavdat Azizov & David H. Russell & Lei Fang & Arthur Laganowsky, 2023. "Polyamine detergents tailored for native mass spectrometry studies of membrane proteins," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    3. 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.

    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:454:y:2008:i:7203:d:10.1038_nature07101. 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.