Cited by 181Neuroscience and Neuropharmacology ResearchReceptor Mechanisms and SignalingNicotinic Acetylcholine Receptors Study

Crystal structures of a GABAA-receptor chimera reveal new endogenous neurosteroid-binding sites.

Open access
Laverty, Duncan, Thomas, Philip, Field, Martin, Andersen, Ole J, Gold, Matthew G, Biggin, Philip C, Gielen, Marc, Smart, Trevor G·2017·Nature Structural & Molecular Biology

Abstract

γ-Aminobutyric acid receptors (GABA A Rs) are vital for controlling excitability in the brain. This is emphasized by the numerous neuropsychiatric disorders that result from receptor dysfunction. A critical component of most native GABA A Rs is the α subunit. Its transmembrane domain is the target for many modulators, including endogenous brain neurosteroids that impact anxiety, stress and depression, and for therapeutic drugs, such as general anesthetics. Understanding the basis for the modulation of GABA A R function requires high-resolution structures. Here we present the first atomic structures of a GABA A R chimera at 2.8-Å resolution, including those bound with potentiating and inhibitory neurosteroids. These structures define new allosteric binding sites for these modulators that are associated with the α-subunit transmembrane domain. Our findings will enable the exploitation of neurosteroids for therapeutic drug design to regulate GABA A Rs in neurological disorders.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/nsmb.3477

Cites

72 of 72 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

1 of the 73 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. [7]Smart TG Paoletti P Synaptic Neurotransmitter-Gated Receptors Sheng M Sabatini BL Sudhof TC The Synapse Cold Spring Harbor Laboratory Press New York 2012 191 216

Cited by

Sorted by citations

Authors
Laverty, D., Thomas, P., Field, M., Andersen, O. J., Gold, M. G., Biggin, P. C., Gielen, M., & Smart, T. G.
Affiliations
  • University College London (GB)
  • University of Oxford (GB)
Corresponding author
Smart, Trevor G
Venue
Nature Structural & Molecular Biology
Published
2017-10-02
Volume
24
Issue
11
Pages
977-985
ISSN
  • 1545-9985 (ISSN-L)
  • 1545-9993
OpenAlex
W2756488677
Cited by
179
References
73
Citations by year
2026: 11 · 2025: 7 · 2024: 15 · 2023: 19 · 2022: 14 · 2021: 31 · 2020: 21 · 2019: 33 · 2018: 26 · 2017: 2
FWCI
10.97
Type
journal article
Language
en
Open access
Locations
  • Nature Structural & Molecular Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • Wellcome Trust (104194/Z/14/Z, 104194)
  • Medical Research Council (MR/K005537/1)
  • Engineering and Physical Sciences Research Council (EP/G042853/1, EP/J003921/1, EP/M022609/1, EP/M027546/1, EP/I030395/1, EP/J010588/1, EP/G007705/1, EP/L000253/1)
  • Biotechnology and Biological Sciences Research Council (BB/L018756/1, BB/K016601/1, BB/N015274/1)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Keywords
GABAA receptor, neurosteroids, allosteric site, chimeric receptors, crystal structure, general anesthetics, GABA receptor modulation, drug design
MeSH terms
Animals, Binding Sites, Models, Molecular, Protein Conformation, Receptors, GABA-A, Recombinant Proteins, Crystallography, X-Ray, Neurotransmitter Agents, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review