IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v549y2017i7670d10.1038_nature23479.html
   My bibliography  Save this article

Channel opening and gating mechanism in AMPA-subtype glutamate receptors

Author

Listed:
  • Edward C. Twomey

    (Columbia University
    Integrated Program in Cellular, Molecular, and Biomedical Studies, Columbia University)

  • Maria V. Yelshanskaya

    (Columbia University)

  • Robert A. Grassucci

    (Columbia University
    Howard Hughes Medical Institute)

  • Joachim Frank

    (Columbia University
    Howard Hughes Medical Institute
    Columbia University)

  • Alexander I. Sobolevsky

    (Columbia University)

Abstract

AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-subtype ionotropic glutamate receptors mediate fast excitatory neurotransmission throughout the central nervous system. Gated by the neurotransmitter glutamate, AMPA receptors are critical for synaptic strength, and dysregulation of AMPA receptor-mediated signalling is linked to numerous neurological diseases. Here we use cryo-electron microscopy to solve the structures of AMPA receptor–auxiliary subunit complexes in the apo, antagonist- and agonist-bound states and determine the iris-like mechanism of ion channel opening. The ion channel selectivity filter is formed by the extended portions of the re-entrant M2 loops, while the helical portions of M2 contribute to extensive hydrophobic interfaces between AMPA receptor subunits in the ion channel. We show how the permeation pathway changes upon channel opening and identify conformational changes throughout the entire AMPA receptor that accompany activation and desensitization. Our findings provide a framework for understanding gating across the family of ionotropic glutamate receptors and the role of AMPA receptors in excitatory neurotransmission.

Suggested Citation

  • Edward C. Twomey & Maria V. Yelshanskaya & Robert A. Grassucci & Joachim Frank & Alexander I. Sobolevsky, 2017. "Channel opening and gating mechanism in AMPA-subtype glutamate receptors," Nature, Nature, vol. 549(7670), pages 60-65, September.
    • Handle: RePEc:nat:nature:v:549:y:2017:i:7670:d:10.1038_nature23479
    DOI: 10.1038/nature23479
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature23479
    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/nature23479?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. Amanda M. Perozzo & Jochen Schwenk & Aichurok Kamalova & Terunaga Nakagawa & Bernd Fakler & Derek Bowie, 2023. "GSG1L-containing AMPA receptor complexes are defined by their spatiotemporal expression, native interactome and allosteric sites," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Beatriz Herguedas & Bianka K. Kohegyi & Jan-Niklas Dohrke & Jake F. Watson & Danyang Zhang & Hinze Ho & Saher A. Shaikh & Remigijus Lape & James M. Krieger & Ingo H. Greger, 2022. "Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Johansen B. Amin & Miaomiao He & Ramesh Prasad & Xiaoling Leng & Huan-Xiang Zhou & Lonnie P. Wollmuth, 2023. "Two gates mediate NMDA receptor activity and are under subunit-specific regulation," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    4. Danyang Zhang & Remigijus Lape & Saher A. Shaikh & Bianka K. Kohegyi & Jake F. Watson & Ondrej Cais & Terunaga Nakagawa & Ingo H. Greger, 2023. "Modulatory mechanisms of TARP γ8-selective AMPA receptor therapeutics," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    5. Madeleine R. Wilcox & Aparna Nigam & Nathan G. Glasgow & Chamali Narangoda & Matthew B. Phillips & Dhilon S. Patel & Samaneh Mesbahi-Vasey & Andreea L. Turcu & Santiago Vázquez & Maria G. Kurnikova & , 2022. "Inhibition of NMDA receptors through a membrane-to-channel path," Nature Communications, Nature, vol. 13(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:nature:v:549:y:2017:i:7670:d:10.1038_nature23479. 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.