ArticleBiophysical journal2013
Coupled global and local changes direct substrate translocation by neurotransmitter-sodium symporter ortholog LeuT.
Article in Biophysical journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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.
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.
Who cites it
41 citing papers in PubMed, 55 citations in OpenAlex.
- From extracellular entry to intracellular release: A water-assisted transport cycle for creatine in SLC6A8.Protein science : a publication of the Protein Society · 2026Article
- Substrate Binding and Conformational Dynamics of the Monoamine Transporters.Advances in neurobiology · 2025Review
- Allosteric modulation of serotonin and dopamine transporters: New insights from computations and experiments.Current research in physiology · 2024Article
- The Alkylamine Stimulant 1,3-Dimethylamylamine Exhibits Substrate-Like Regulation of Dopamine Transporter Function and Localization.The Journal of pharmacology and experimental therapeutics · 2023Article
- Sodium/Iodide Symporter Metastable Intermediates Provide Insights into Conformational Transition between Principal Thermodynamic States.The journal of physical chemistry. B · 2023Article
- Allosteric Modulator KM822 Attenuates Behavioral Actions of Amphetamine inMolecular pharmacology · 2022Article
- The substrate import mechanism of the human serotonin transporter.Biophysical journal · 2022Article
- Allosterically Linked Binding Sites in Serotonin Transporter Revealed by Single Molecule Force Spectroscopy.Frontiers in molecular biosciences · 2020Review
- The allosteric mechanism of substrate-specific transport in SLC6 is mediated by a volumetric sensor.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Monoamine transporters: structure, intrinsic dynamics and allosteric regulation.Nature structural & molecular biology · 2019Review
- Shared dynamics of LeuT superfamily members and allosteric differentiation by structural irregularities and multimerization.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018Article
- Quantitative Assessment of the Energetics of Dopamine Translocation by Human Dopamine Transporter.The journal of physical chemistry. B · 2018Article
- Thermodynamic Coupling Function Analysis of Allosteric Mechanisms in the Human Dopamine Transporter.Biophysical journal · 2018Article
- Article
- Allosteric modulation of human dopamine transporter activity under conditions promoting its dimerization.The Journal of biological chemistry · 2017Article
- Substrate transport and anion permeation proceed through distinct pathways in glutamate transporters.eLife · 2017Article
- Effect of Dimerization on the Dynamics of Neurotransmitter:Sodium Symporters.The journal of physical chemistry. B · 2017Article
- Atomistic modeling of alternating access of a mitochondrial ADP/ATP membrane transporter with molecular simulations.PloS one · 2017Article
- The Environment Shapes the Inner Vestibule of LeuT.PLoS computational biology · 2016Article
- Conformational Dynamics on the Extracellular Side of LeuT Controlled by Na+ and K+ Ions and the Protonation State of Glu290.The Journal of biological chemistry · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Significant advances have been made in recent years in characterizing neurotransmitter:sodium symporter (NSS) family structure and function. Yet, many time-resolved events and intermediates that control the various stages of transport cycle remain to be elucidated. Whether NSSs harbor one or two sites for binding their substrates (neurotransmitters or amino acids), and what the role of the secondary site S2 is, if any, are still unresolved. Using molecular modeling and simulations for LeuT, a bacterial NSS, we present a comprehensive account of substrate-binding and -stabilization events, and subsequently triggered interactions leading to substrate (alanine) release. LeuT instantaneous conformation as it reconfigures from substrate-receiving (outward-facing) to -releasing (inward-facing) state appears to be a determinant of its affinity to bind substrate at site S2. In the outward-facing state, S1 robustly binds alanine and regulates subsequent redistribution of interactions to trigger extracellular gate closure; whereas S2 is only a transient binding site. The substrate-binding affinity at S2 increases in an intermediate close to inward-facing state. LeuT harbors the two substrate-binding sites, and small displacements of second substrate near S2 are observed to induce concerted small translocations in the substrate bound to primary site S1, although complete release requires collective structural rearrangements that fully expose the intracellular vestibule to the cytoplasm.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.