ArticleNature structural & molecular biology2014
Conformational dynamics of ligand-dependent alternating access in LeuT.
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 100 papers.
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Who cites it
100 citing papers in PubMed, 155 citations in OpenAlex.
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- Cell membrane cholesterol affects serotonin transporter efflux due to altered transporter oligomerization.Molecular psychiatry · 2026Article
- Protein Modeling with DEER Spectroscopy.Annual review of biophysics · 2025Review
- 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
- Monitoring conformational changes in the human neurotransmitter transporter homologue LeuT withJournal of neurochemistry · 2025Article
- Substrate Binding and Conformational Dynamics of the Monoamine Transporters.Advances in neurobiology · 2025Review
- CHARMM at 45: Enhancements in Accessibility, Functionality, and Speed.The journal of physical chemistry. B · 2024Review
- 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
- They all rock: A systematic comparison of conformational movements in LeuT-fold transporters.Structure (London, England : 1993) · 2024Article
- Article
- Single-Molecule Imaging of Integral Membrane Protein Dynamics and Function.Annual review of biophysics · 2024Review
- Cholesterol modulation of interactions between psychostimulants and dopamine transporters.Advances in pharmacology (San Diego, Calif.) · 2024Article
- Tackling Hysteresis in Conformational Sampling: How to Be Forgetful with MEMENTO.Journal of chemical theory and computation · 2023Article
- A novel approach to modeling side chain ensembles of the bifunctional spin label RX.bioRxiv : the preprint server for biology · 2023Article
- Structure-based discovery of conformationally selective inhibitors of the serotonin transporter.Cell · 2023Article
- Hydrogen/deuterium exchange-mass spectrometry of integral membrane proteins in native-like environments: current scenario and the way forward.Essays in biochemistry · 2023Article
- Atorvastatin differentially regulates the interactions of cocaine and amphetamine with dopamine transporters.Neuropharmacology · 2023Article
- Cryo-EM structure of the human NKCC1 transporter reveals mechanisms of ion coupling and specificity.The EMBO journal · 2022Article
- Determining Ligand and Ion-Induced Conformational Changes in Serotonin Transporter with Its Fluorescent Substrates.International journal of molecular sciences · 2022Article
40 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
The leucine transporter (LeuT) from Aquifex aeolicus is a bacterial homolog of neurotransmitter/sodium symporters (NSSs) that catalyze reuptake of neurotransmitters at the synapse. Crystal structures of wild-type and mutants of LeuT have been interpreted as conformational states in the coupled transport cycle. However, the mechanistic identities inferred from these structures have not been validated, and the ligand-dependent conformational equilibrium of LeuT has not been defined. Here, we used distance measurements between spin-label pairs to elucidate Na(+)- and leucine-dependent conformational changes on the intracellular and extracellular sides of the transporter. The results identify structural motifs that underlie the isomerization of LeuT between outward-facing, inward-facing and occluded states. The conformational changes reported here present a dynamic picture of the alternating-access mechanism of LeuT and NSSs that is different from the inferences reached from currently available structural models.
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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.