IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v559y2018i7712d10.1038_s41586-018-0255-3.html
   My bibliography  Save this article

Structure of a human synaptic GABAA receptor

Author

Listed:
  • Shaotong Zhu

    (University of Texas Southwestern Medical Center)

  • Colleen M. Noviello

    (University of Texas Southwestern Medical Center)

  • Jinfeng Teng

    (University of Texas Southwestern Medical Center)

  • Richard M. Walsh

    (University of Texas Southwestern Medical Center)

  • Jeong Joo Kim

    (University of Texas Southwestern Medical Center)

  • Ryan E. Hibbs

    (University of Texas Southwestern Medical Center)

Abstract

Fast inhibitory neurotransmission in the brain is principally mediated by the neurotransmitter GABA (γ-aminobutyric acid) and its synaptic target, the type A GABA receptor (GABAA receptor). Dysfunction of this receptor results in neurological disorders and mental illnesses including epilepsy, anxiety and insomnia. The GABAA receptor is also a prolific target for therapeutic, illicit and recreational drugs, including benzodiazepines, barbiturates, anaesthetics and ethanol. Here we present high-resolution cryo-electron microscopy structures of the human α1β2γ2 GABAA receptor, the predominant isoform in the adult brain, in complex with GABA and the benzodiazepine site antagonist flumazenil, the first-line clinical treatment for benzodiazepine overdose. The receptor architecture reveals unique heteromeric interactions for this important class of inhibitory neurotransmitter receptor. This work provides a template for understanding receptor modulation by GABA and benzodiazepines, and will assist rational approaches to therapeutic targeting of this receptor for neurological disorders and mental illness.

Suggested Citation

  • Shaotong Zhu & Colleen M. Noviello & Jinfeng Teng & Richard M. Walsh & Jeong Joo Kim & Ryan E. Hibbs, 2018. "Structure of a human synaptic GABAA receptor," Nature, Nature, vol. 559(7712), pages 67-72, July.
  • Handle: RePEc:nat:nature:v:559:y:2018:i:7712:d:10.1038_s41586-018-0255-3
    DOI: 10.1038/s41586-018-0255-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41586-018-0255-3
    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/s41586-018-0255-3?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. Arvind Kumar & Kayla Kindig & Shanlin Rao & Afroditi-Maria Zaki & Sandip Basak & Mark S. P. Sansom & Philip C. Biggin & Sudha Chakrapani, 2022. "Structural basis for cannabinoid-induced potentiation of alpha1-glycine receptors in lipid nanodiscs," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Weronika Chojnacka & Jinfeng Teng & Jeong Joo Kim & Anders A. Jensen & Ryan E. Hibbs, 2024. "Structural insights into GABAA receptor potentiation by Quaalude," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    3. Dagimhiwat H. Legesse & Chen Fan & Jinfeng Teng & Yuxuan Zhuang & Rebecca J. Howard & Colleen M. Noviello & Erik Lindahl & Ryan E. Hibbs, 2023. "Structural insights into opposing actions of neurosteroids on GABAA receptors," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    4. Yingfeng Tao & Xiaoliu Zhou & Leqiang Sun & Da Lin & Huaiyuan Cai & Xi Chen & Wei Zhou & Bing Yang & Zhe Hu & Jing Yu & Jing Zhang & Xiaoqing Yang & Fang Yang & Bang Shen & Wenbao Qi & Zhenfang Fu & J, 2023. "Highly efficient and robust π-FISH rainbow for multiplexed in situ detection of diverse biomolecules," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. Shaotong Zhu & Akshay Sridhar & Jinfeng Teng & Rebecca J. Howard & Erik Lindahl & Ryan E. Hibbs, 2022. "Structural and dynamic mechanisms of GABAA receptor modulators with opposing activities," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    6. Marie S. Prevost & Nathalie Barilone & Gabrielle Dejean de la Bâtie & Stéphanie Pons & Gabriel Ayme & Patrick England & Marc Gielen & François Bontems & Gérard Pehau-Arnaudet & Uwe Maskos & Pierre , 2023. "An original potentiating mechanism revealed by the cryo-EM structures of the human α7 nicotinic receptor in complex with nanobodies," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    7. Emma Rie Olander & Dieter Janzen & Carmen Villmann & Anders A Jensen, 2020. "Comparison of biophysical properties of α1β2 and α3β2 GABAA receptors in whole-cell patch-clamp electrophysiological recordings," PLOS ONE, Public Library of Science, vol. 15(6), pages 1-13, June.

    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:559:y:2018:i:7712:d:10.1038_s41586-018-0255-3. 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.