ArticleNature structural & molecular biology2023
Molecular basis for substrate recognition and transport of human GABA transporter GAT1.
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 37 papers.
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Who cites it
37 citing papers in PubMed, 53 citations in OpenAlex.
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- From extracellular entry to intracellular release: A water-assisted transport cycle for creatine in SLC6A8.Protein science : a publication of the Protein Society · 2026Article
- In Silico Selection of GAT-1 Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2026Article
- 4 Phenylbutyrate Plus Gene augmentation: A Dual Therapy To Rescue of SLC6A1 Variant Associated Developmental And Epileptic Encephalopathy.bioRxiv : the preprint server for biology · 2026Article
- The role of γ-aminobutyric acid and its receptor in metabolic reprogramming and tumor progression.Biochemistry and biophysics reports · 2026Review
- A Novel Role of Dexmedetomidine in the Modulation of Morphine Reward Memory via γ-Aminobutyric Acid Transporter-1.Anesthesiology · 2026Article
- Substrate recognition and allosteric inhibition of human betaine/GABA transporter 1.Nature communications · 2026Article
- Structural mechanism of substrate binding and inhibition of human taurine transporter.Nature communications · 2026Article
- Structural basis for selective inhibition of human GABA transporter GAT3.Nature communications · 2026Article
- Cardiac endogenous transmitter system: molecular features, functions, and clinical implications.European heart journal · 2026Review
- Unveiling the Structure of PROT and ATBMolecules (Basel, Switzerland) · 2025Article
- Uncovering hidden protein modifications with native top-down mass spectrometry.Nature methods · 2025Article
- 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 · 2025Article
- Molecular basis of human taurine transporter uptake and inhibition.Nature communications · 2025Article
- Molecular basis for substrate recognition and transport of mammalian taurine transporters.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Dimerization and substrate recognition of human taurine transporter.Nature communications · 2025Article
- Preoperative Sleep Deprivation Exacerbates Anesthesia/Surgery-induced Abnormal GABAergic Neurotransmission and Neuronal Damage in the Hippocampus in Aged Mice.Molecular neurobiology · 2025Article
- 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 · 2025Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
γ-Aminobutyric acid (GABA), an important inhibitory neurotransmitter in the central nervous system, is recycled through specific GABA transporters (GATs). GAT1, which is mainly expressed in the presynaptic terminals of axons, is a potential drug target of neurological disorders due to its essential role in GABA transport. Here we report four cryogenic electron microscopy structures of human GAT1, at resolutions of 2.2-3.2 Å. GAT1 in substrate-free form or in complex with the antiepileptic drug tiagabine exhibits an inward-open conformation. In the presence of GABA or nipecotic acid, inward-occluded structures are captured. The GABA-bound structure reveals an interaction network bridged by hydrogen bonds and ion coordination for GABA recognition. The substrate-free structure unwinds the last helical turn of transmembrane helix TM1a to release sodium ions and substrate. Complemented by structure-guided biochemical analyses, our studies reveal detailed mechanism of GABA recognition and transport, and elucidate mode of action of the inhibitors, nipecotic acid and tiagabine.
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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.