ArticleBiophysical journal2015
Properties of an inward-facing state of LeuT: conformational stability and substrate release.
Article in Biophysical journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- Structural mechanism of substrate binding and inhibition of human taurine transporter.Nature communications · 2026Article
- Single-Molecule Imaging of Integral Membrane Protein Dynamics and Function.Annual review of biophysics · 2024Review
- Tackling Hysteresis in Conformational Sampling: How to Be Forgetful with MEMENTO.Journal of chemical theory and computation · 2023Article
- Integrated AlphaFold2 and DEER investigation of the conformational dynamics of a pH-dependent APC antiporter.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Illumination of serotonin transporter mechanism and role of the allosteric site.Science advances · 2021Article
- The antidepressant drug vilazodone is an allosteric inhibitor of the serotonin transporter.Nature communications · 2021Article
- Transmembrane helix 6b links proton and metal release pathways and drives conformational change in an Nramp-family transition metal transporter.The Journal of biological chemistry · 2020Article
- Serotonin transport in the 21st century.The Journal of general physiology · 2019Review
- Characterization of Lipid-Protein Interactions and Lipid-Mediated Modulation of Membrane Protein Function through Molecular Simulation.Chemical reviews · 2019Review
- Dopamine transporter oligomerization involves the scaffold domain, but spares the bundle domain.PLoS computational biology · 2018Article
- Structural insights into the elevator-like mechanism of the sodium/citrate symporter CitS.Scientific reports · 2017Article
- Effect of Dimerization on the Dynamics of Neurotransmitter:Sodium Symporters.The journal of physical chemistry. B · 2017Article
- Conformational dynamics of a neurotransmitter:sodium symporter in a lipid bilayer.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Crystal Structure and Conformational Change Mechanism of a Bacterial Nramp-Family Divalent Metal Transporter.Structure (London, England : 1993) · 2016Article
- The Environment Shapes the Inner Vestibule of LeuT.PLoS computational biology · 2016Article
- Two Na+ Sites Control Conformational Change in a Neurotransmitter Transporter Homolog.The Journal of biological chemistry · 2016Article
- Energy landscape of LeuT from molecular simulations.The Journal of chemical physics · 2015Article
- Mechanism of Na(+)-dependent citrate transport from the structure of an asymmetrical CitS dimer.eLife · 2015Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The leucine transporter (LeuT) is a bacterial homolog of the human monoamine transporters, which are important pharmaceutical targets. There are no high-resolution structures of the human transporters available; however, LeuT has been crystallized in several different conformational states. Recently, an inward-facing conformation of LeuT was solved revealing an unexpectedly large movement of transmembrane helix 1a (TM1a). We have performed molecular dynamics simulations of the mutated and wild-type transporter, with and without the cocrystallized Fab antibody fragment, to investigate the properties of this inward-facing conformation in relation to transport by LeuT within the membrane environment. In all of the simulations, local conformational changes with respect to the crystal structure are consistently observed, especially in TM1a. Umbrella sampling revealed a soft potential for TM1a tilting. Furthermore, simulations of inward-facing LeuT with Na(+) ions and substrate bound suggest that one of the Na(+) ion binding sites is fully disrupted. Release of alanine and the second Na(+) ion is also observed, giving insight into the final stage of the translocation process in atomistic detail.
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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.