Evidence map›Paper›PMID 37400654›Full record

ArticleNature structural & molecular biology2023

Cryo-EM structure of GABA transporter 1 reveals substrate recognition and transport mechanism.

Smruti Ranjan Nayak, Deepthi Joseph, Georg Höfner, Archishman Dakua, Arunabh Athreya, Klaus T Wanner, Baruch I Kanner, Aravind Penmatsa

Abstract read
In one paragraph

Article in Nature structural & molecular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed.

  1. Article
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  5. Review
  6. Article
  7. Article
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  9. Article
  10. Structural insights into the substrate uptake and inhibition of the human creatine transporter (hCRT).Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  11. Article
  12. A New GlyT2 Variant Associated with Hyperekplexia.International journal of molecular sciences · 2025
    Article
  13. Molecular basis for substrate recognition and transport of mammalian taurine transporters.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  14. Article
  15. Rescue of Epilepsy-Associated Mutations of the Highly Conserved Glycine Residue 443 in the Human GABA Transporter 1.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. Computational and structural biotechnology journal · 2024
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Smruti Ranjan Nayak *Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.
Deepthi Joseph *Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India.ORCID 0000-0001-8913-9225
Georg HöfnerDepartment of Pharmacy, Center for Drug Research, Ludwig Maximilians University of Munich, Munich, Germany.
Archishman DakuaMolecular Biophysics Unit, Indian Institute of Science, Bangalore, India.ORCID 0000-0003-1727-772X
Arunabh AthreyaMolecular Biophysics Unit, Indian Institute of Science, Bangalore, India.ORCID 0000-0003-2133-2795
Klaus T WannerDepartment of Pharmacy, Center for Drug Research, Ludwig Maximilians University of Munich, Munich, Germany.
Baruch I KannerDepartment of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada, Hebrew University, Hadassah Medical School, Jerusalem, Israel.
Aravind PenmatsaMolecular Biophysics Unit, Indian Institute of Science, Bangalore, India. penmatsa@iisc.ac.in.ORCID 0000-0001-9519-5055

Funding

Biotechnology and Biological Sciences Research CouncilDBT-Wellcome Trust India Alliance IA/S/22/1/506242Medical Research CouncilWellcome Trust
6 · The paper itself

Abstract

The inhibitory neurotransmitter γ-aminobutyric acid (GABA) is cleared from the synaptic cleft by the sodium- and chloride-coupled GABA transporter GAT1. Inhibition of GAT1 prolongs the GABAergic signaling at the synapse and is a strategy to treat certain forms of epilepsy. In this study, we present the cryo-electron microscopy structure of Rattus norvegicus GABA transporter 1 (rGAT1) at a resolution of 3.1 Å. The structure elucidation was facilitated by epitope transfer of a fragment-antigen binding (Fab) interaction site from the Drosophila dopamine transporter (dDAT) to rGAT1. The structure reveals rGAT1 in a cytosol-facing conformation, with a linear density in the primary binding site that accommodates a molecule of GABA, a displaced ion density proximal to Na site 1 and a bound chloride ion. A unique insertion in TM10 aids the formation of a compact, closed extracellular gate. Besides yielding mechanistic insights into ion and substrate recognition, our study will enable the rational design of specific antiepileptics.

Indexed as

Chloridesgamma-Aminobutyric AcidAnimalsBinding SitesCryoelectron MicroscopyGABA Plasma Membrane Transport ProteinsRatsChloridesGABA Plasma Membrane Transport Proteinsgamma-Aminobutyric Acid

Identifiers

PMID37400654
PMCPMC10352132

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.