Evidence map›Paper›PMID 42156742›Full record

ArticleNature communications2026

Substrate recognition and allosteric inhibition of human betaine/GABA transporter 1.

Jun Zhou, Jiameng Liu, Yuchen Jin, Qianyu Wang, Haibo Yu, Jing-Xiang Wu

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

6 authors.

Jun Zhou *State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P. R. China.ORCID http://orcid.org/0009-0007-0103-2476
Jiameng Liu *State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P. R. China.ORCID http://orcid.org/0009-0006-1088-2299
Yuchen JinState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P. R. China.
Qianyu WangState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P. R. China.
Haibo YuState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P. R. China. haiboyu@imm.ac.cn.
Jing-Xiang WuState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, P. R. China. wujingxiang@imm.ac.cn.ORCID http://orcid.org/0000-0001-9851-0065

Funding

National Natural Science Foundation of China (National Science Foundation of China) 32522046
6 · The paper itself

Abstract

The betaine/GABA transporter 1 (BGT1, SLC6A12) regulates neurotransmitter clearance and osmotic balance by transporting GABA and betaine in a sodium- and chloride-dependent manner. BGT1 has become a promising target for epilepsy treatment due to the anticonvulsant effects observed with BGT1 inhibitors. Although BGT1 plays key roles in both renal and neuronal physiology, the molecular basis of its substrate recognition and inhibition remains unclear. Here, we report cryo-EM structures of human BGT1 in the apo form and in complex with GABA, betaine, the substrate-like inhibitor ATPCA, and the selective inhibitor BPDBA all without the use of fiducial markers. These structures capture BGT1 in both occluded and inward-facing conformations, delineating the conformational transitions associated with substrate release. BPDBA binds to an intracellular cavity adjacent to the intracellular gate. This binding mode locks TM1a to transit and inhibits substrate release. Together, our results uncover distinct mechanisms of substrate recognition and allosteric inhibition of hBGT1, offering structural insights for the development of hBGT1-selective modulators.

Indexed as

GABA Plasma Membrane Transport ProteinsAllosteric RegulationBetaineCryoelectron Microscopygamma-Aminobutyric AcidHumansModels, MolecularProtein BindingProtein ConformationSubstrate SpecificityBetainebetaine plasma membrane transport proteinsGABA Plasma Membrane Transport Proteinsgamma-Aminobutyric Acid

Identifiers

PMID42156742
PMCPMC13381564

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.