IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms5189.html
   My bibliography  Save this article

Relative motions between left flipper and dorsal fin domains favour P2X4 receptor activation

Author

Listed:
  • Wen-Shan Zhao

    (Shanghai Jiao Tong University School of Medicine
    Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University)

  • Jin Wang

    (Shanghai Jiao Tong University School of Medicine)

  • Xiao-Juan Ma

    (Shanghai Jiao Tong University School of Medicine
    Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University)

  • Yang Yang

    (Shanghai Jiao Tong University School of Medicine)

  • Yan Liu

    (Shanghai Jiao Tong University School of Medicine)

  • Li-Dong Huang

    (Shanghai Jiao Tong University School of Medicine)

  • Ying-Zhe Fan

    (Putuo District Center Hospital, Shanghai University of Chinese Traditional Medicine)

  • Xiao-Yang Cheng

    (Shanghai Jiao Tong University School of Medicine)

  • Hong-Zhuan Chen

    (Shanghai Jiao Tong University School of Medicine)

  • Rui Wang

    (Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University)

  • Ye Yu

    (Shanghai Jiao Tong University School of Medicine
    College of Bioscience and Biotechnology, Hunan Agricultural University)

Abstract

Channel gating in response to extracellular ATP is a fundamental process for the physiological functions of P2X receptors. Here we identify coordinated allosteric changes in the left flipper (LF) and dorsal fin (DF) domains that couple ATP-binding to channel gating. Engineered disulphide crosslinking or zinc bridges between the LF and DF domains that constrain their relative motions significantly influence channel gating of P2X4 receptors, confirming the essential role of these allosteric changes. ATP-binding-induced alterations in interdomain hydrophobic interactions among I208, L217, V291 and the aliphatic chain of K193 correlate well with these coordinated relative movements. Mutations on those four residues lead to impaired or fully abolished channel activations of P2X4 receptors. Our data reveal that ATP-binding-induced altered interdomain hydrophobic interactions and the concomitant coordinated motions of LF and DF domains are allosteric events essential for the channel gating of P2X4 receptors.

Suggested Citation

  • Wen-Shan Zhao & Jin Wang & Xiao-Juan Ma & Yang Yang & Yan Liu & Li-Dong Huang & Ying-Zhe Fan & Xiao-Yang Cheng & Hong-Zhuan Chen & Rui Wang & Ye Yu, 2014. "Relative motions between left flipper and dorsal fin domains favour P2X4 receptor activation," Nature Communications, Nature, vol. 5(1), pages 1-11, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5189
    DOI: 10.1038/ncomms5189
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms5189
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms5189?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:5:y:2014:i:1:d:10.1038_ncomms5189. 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.