ArticlePLoS computational biology2014
Complete mapping of substrate translocation highlights the role of LeuT N-terminal segment in regulating transport cycle.
Article in PLoS computational biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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
42 citing papers in PubMed, 66 citations in OpenAlex.
- Monitoring conformational changes in the human neurotransmitter transporter homologue LeuT withJournal of neurochemistry · 2025Article
- The Alkylamine Stimulant 1,3-Dimethylamylamine Exhibits Substrate-Like Regulation of Dopamine Transporter Function and Localization.The Journal of pharmacology and experimental therapeutics · 2023Article
- The substrate import mechanism of the human serotonin transporter.Biophysical journal · 2022Article
- Functional Characterization of the Dopaminergic Psychostimulant Sydnocarb as an Allosteric Modulator of the Human Dopamine Transporter.Biomedicines · 2021Article
- Article
- The Amino Terminus of LeuT Changes Conformation in an Environment Sensitive Manner.Neurochemical research · 2020Article
- Mapping of Ion and Substrate Binding Sites in Human Sodium Iodide Symporter (hNIS).Journal of chemical information and modeling · 2020Article
- X-ray structure of LeuT in an inward-facing occluded conformation reveals mechanism of substrate release.Nature communications · 2020Article
- Trimerization of dopamine transporter triggered by AIM-100 binding: Molecular mechanism and effect of mutations.Neuropharmacology · 2019Article
- In silico characterization of residues essential for substrate binding of human cystine transporter, xCT.Journal of molecular modeling · 2019Article
- Advances and Challenges in Rational Drug Design for SLCs.Trends in pharmacological sciences · 2019Review
- Shared Signature Dynamics Tempered by Local Fluctuations Enables Fold Adaptability and Specificity.Molecular biology and evolution · 2019Article
- Monoamine transporters: structure, intrinsic dynamics and allosteric regulation.Nature structural & molecular biology · 2019Review
- Tales of tails in transporters.Open biology · 2019Review
- Multiscale Simulations of Biological Membranes: The Challenge To Understand Biological Phenomena in a Living Substance.Chemical reviews · 2019Article
- 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
- How structural elements evolving from bacterial to human SLC6 transporters enabled new functional properties.BMC biology · 2018Article
- Latch and trigger role for R445 in DAT transport explains molecular basis of DTDS.Bioorganic & medicinal chemistry letters · 2018Article
- A partially-open inward-facing intermediate conformation of LeuT is associated with NaNature communications · 2018Article
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
Neurotransmitter: sodium symporters (NSSs) regulate neuronal signal transmission by clearing excess neurotransmitters from the synapse, assisted by the co-transport of sodium ions. Extensive structural data have been collected in recent years for several members of the NSS family, which opened the way to structure-based studies for a mechanistic understanding of substrate transport. Leucine transporter (LeuT), a bacterial orthologue, has been broadly adopted as a prototype in these studies. This goal has been elusive, however, due to the complex interplay of global and local events as well as missing structural data on LeuT N-terminal segment. We provide here for the first time a comprehensive description of the molecular events leading to substrate/Na+ release to the postsynaptic cell, including the structure and dynamics of the N-terminal segment using a combination of molecular simulations. Substrate and Na+-release follows an influx of water molecules into the substrate/Na+-binding pocket accompanied by concerted rearrangements of transmembrane helices. A redistribution of salt bridges and cation-π interactions at the N-terminal segment prompts substrate release. Significantly, substrate release is followed by the closure of the intracellular gate and a global reconfiguration back to outward-facing state to resume the transport cycle. Two minimally hydrated intermediates, not structurally resolved to date, are identified: one, substrate-bound, stabilized during the passage from outward- to inward-facing state (holo-occluded), and another, substrate-free, along the reverse transition (apo-occluded).
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.