IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms5733.html
   My bibliography  Save this article

Activation of G-protein-coupled receptors correlates with the formation of a continuous internal water pathway

Author

Listed:
  • Shuguang Yuan

    (Laboratory of Physical Chemistry of Polymers and Membranes, École Polytechnique Fédérale de Lausanne
    Present address: Actelion Pharmaceuticals Ltd, 4123 Basel, Switzerland)

  • Slawomir Filipek

    (Laboratory of Biomodeling, Faculty of Chemistry & Biological and Chemical Research Centre, University of Warsaw)

  • Krzysztof Palczewski

    (School of Medicine, Case Western Reserve University)

  • Horst Vogel

    (Laboratory of Physical Chemistry of Polymers and Membranes, École Polytechnique Fédérale de Lausanne)

Abstract

Recent crystal structures of G-protein-coupled receptors (GPCRs) have revealed ordered internal water molecules, raising questions about the functional role of those waters for receptor activation that could not be answered by the static structures. Here, we used molecular dynamics simulations to monitor—at atomic and high temporal resolution—conformational changes of central importance for the activation of three prototypical GPCRs with known crystal structures: the adenosine A2A receptor, the β2-adrenergic receptor and rhodopsin. Our simulations reveal that a hydrophobic layer of amino acid residues next to the characteristic NPxxY motif forms a gate that opens to form a continuous water channel only upon receptor activation. The highly conserved tyrosine residue Y7.53 undergoes transitions between three distinct conformations representative of inactive, G-protein activated and GPCR metastates. Additional analysis of the available GPCR crystal structures reveals general principles governing the functional roles of internal waters in GPCRs.

Suggested Citation

  • Shuguang Yuan & Slawomir Filipek & Krzysztof Palczewski & Horst Vogel, 2014. "Activation of G-protein-coupled receptors correlates with the formation of a continuous internal water pathway," Nature Communications, Nature, vol. 5(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5733
    DOI: 10.1038/ncomms5733
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms5733
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms5733?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. Xiaohu Hu & Yibo Wang & Amanda Hunkele & Davide Provasi & Gavril W Pasternak & Marta Filizola, 2019. "Kinetic and thermodynamic insights into sodium ion translocation through the μ-opioid receptor from molecular dynamics and machine learning analysis," PLOS Computational Biology, Public Library of Science, vol. 15(1), pages 1-19, January.
    3. 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.

    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:5:y:2014:i:1:d:10.1038_ncomms5733. 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.