ArticleNature structural & molecular biology2014
A mechanism for intracellular release of Na+ by neurotransmitter/sodium symporters.
Article in Nature structural & molecular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers.
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Who cites it
125 citing papers in PubMed.
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- Structural basis for selective inhibition of human GABA transporter GAT3.Nature communications · 2026Article
- A reversible allosteric inhibitor of GlyT2 alleviates neuropathic pain without on-target side effects.bioRxiv : the preprint server for biology · 2025Article
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- Dimerization and substrate recognition of human taurine transporter.Nature communications · 2025Article
- The macromolecular crystallography beamlines of the Helmholtz-Zentrum Berlin at the BESSY II storage ring: history, current status and future directions.Journal of synchrotron radiation · 2025Article
- Molecular basis of human GABA transporter 3 inhibition.Nature communications · 2025Article
- Control of Conformational Transitions by the Conserved GXInternational journal of molecular sciences · 2025Article
- Exploring the Structural Dynamics of LeuT Using EPR Spectroscopy: A Focus on Transmembrane Helix 10.Journal of neurochemistry · 2025Article
- Aromatic Amino Acid Metabolites: Molecular Messengers Bridging Immune-Microbiota Communication.Immune network · 2025Review
- Pharmacological Mechanisms of SLC6 Neurotransmitter Transporter Inhibition.Advances in neurobiology · 2025Review
- The conserved lysine residue in transmembrane helix 5 is pivotal for the cytoplasmic gating of the L-amino acid transporters.PNAS nexus · 2025Article
- Alternating access of a bacterial homolog of neurotransmitter: sodium symporters determined from AlphaFold2 ensembles and DEER spectroscopy.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Cryo-EM structure of the dopamine transporter with a novel atypical non-competitive inhibitor bound to the orthosteric site.Journal of neurochemistry · 2024Article
- Single-Molecule Imaging of Integral Membrane Protein Dynamics and Function.Annual review of biophysics · 2024Review
- Structure and function of the SIT1 proline transporter in complex with the COVID-19 receptor ACE2.Nature communications · 2024Article
65 more citing papers are in PubMed but not listed here.
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7 authors.
Funding
Abstract
Neurotransmitter/sodium symporters (NSSs) terminate synaptic signal transmission by Na+-dependent reuptake of released neurotransmitters. Key conformational states have been reported for the bacterial homolog LeuT and an inhibitor-bound Drosophila dopamine transporter. However, a coherent mechanism of Na+-driven transport has not been described. Here, we present two crystal structures of MhsT, an NSS member from Bacillus halodurans, in occluded inward-facing states with bound Na+ ions and L-tryptophan, providing insight into the cytoplasmic release of Na+. The switch from outward- to inward-oriented states is centered on the partial unwinding of transmembrane helix 5, facilitated by a conserved GlyX9Pro motif that opens an intracellular pathway for water to access the Na2 site. We propose a mechanism, based on our structural and functional findings, in which solvation through the TM5 pathway facilitates Na+ release from Na2 and the transition to an inward-open state.
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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.