Structure of a human synaptic GABAA receptor

Shaotong Zhu, Colleen M. Noviello, Jinfeng Teng, Richard M. Walsh, Jeong Joo Kim and Ryan E. Hibbs ()
Additional contact information
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

Nature, 2018, vol. 559, issue 7712, 67-72

Abstract: 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.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (7)

Downloads: (external link)
https://www.nature.com/articles/s41586-018-0255-3 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:559:y:2018:i:7712:d:10.1038_s41586-018-0255-3

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-018-0255-3

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().