IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v552y2017i7684d10.1038_nature24997.html
   My bibliography  Save this article

Structures of the calcium-activated, non-selective cation channel TRPM4

Author

Listed:
  • Jiangtao Guo

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

  • Ji She

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

  • Weizhong Zeng

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center
    Howard Hughes Medical Institute, University of Texas Southwestern Medical Center)

  • Qingfeng Chen

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center
    Howard Hughes Medical Institute, University of Texas Southwestern Medical Center)

  • Xiao-chen Bai

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

  • Youxing Jiang

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center
    Howard Hughes Medical Institute, University of Texas Southwestern Medical Center)

Abstract

TRPM4 is a calcium-activated, phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) -modulated, non-selective cation channel that belongs to the family of melastatin-related transient receptor potential (TRPM) channels. Here we present the electron cryo-microscopy structures of the mouse TRPM4 channel with and without ATP. TRPM4 consists of multiple transmembrane and cytosolic domains, which assemble into a three-tiered architecture. The N-terminal nucleotide-binding domain and the C-terminal coiled-coil participate in the tetrameric assembly of the channel; ATP binds at the nucleotide-binding domain and inhibits channel activity. TRPM4 has an exceptionally wide filter but is only permeable to monovalent cations; filter residue Gln973 is essential in defining monovalent selectivity. The S1–S4 domain and the post-S6 TRP domain form the central gating apparatus that probably houses the Ca2+- and PtdIns(4,5)P2-binding sites. These structures provide an essential starting point for elucidating the complex gating mechanisms of TRPM4 and reveal the molecular architecture of the TRPM family.

Suggested Citation

  • Jiangtao Guo & Ji She & Weizhong Zeng & Qingfeng Chen & Xiao-chen Bai & Youxing Jiang, 2017. "Structures of the calcium-activated, non-selective cation channel TRPM4," Nature, Nature, vol. 552(7684), pages 205-209, December.
    • Handle: RePEc:nat:nature:v:552:y:2017:i:7684:d:10.1038_nature24997
    DOI: 10.1038/nature24997
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature24997
    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/nature24997?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.

    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:552:y:2017:i:7684:d:10.1038_nature24997. 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.