ArticleThe Journal of biological chemistry2015
Substrate-induced unlocking of the inner gate determines the catalytic efficiency of a neurotransmitter:sodium symporter.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Multiple Pendants-Bearing Triglucosides for Membrane Protein Studies: Effects of Pendant Length and Number on Micelle Interior Hydration and Protein Stability.Biomacromolecules · 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
- Technologies, strategies, and cautions when deconvoluting genome-wide association signals: FTO in focus.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2023Review
- Conformationally flexible core-bearing detergents with a hydrophobic or hydrophilic pendant: Effect of pendant polarity on detergent conformation and membrane protein stability.Acta biomaterialia · 2021Article
- The Amino Terminus of LeuT Changes Conformation in an Environment Sensitive Manner.Neurochemical research · 2020Article
- X-ray structure of LeuT in an inward-facing occluded conformation reveals mechanism of substrate release.Nature communications · 2020Article
- 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
- Substrate-induced conformational dynamics of the dopamine transporter.Nature communications · 2019Article
- Conformational dynamics of the human serotonin transporter during substrate and drug binding.Nature communications · 2019Article
- Article
- Loss of specificity variants of WzxC suggest that substrate recognition is coupled with transporter opening in MOP-family flippases.Molecular microbiology · 2018Article
- The LeuT-fold neurotransmitter:sodium symporter MhsT has two substrate sites.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Substrate-modulated unwinding of transmembrane helices in the NSS transporter LeuT.Science advances · 2018Article
- A partially-open inward-facing intermediate conformation of LeuT is associated with NaNature communications · 2018Article
- Thermodynamic Coupling Function Analysis of Allosteric Mechanisms in the Human Dopamine Transporter.Biophysical journal · 2018Article
- The Isomeric Preference of an Atypical Dopamine Transporter Inhibitor Contributes to Its Selection of the Transporter Conformation.ACS chemical neuroscience · 2017Article
- The role of transmembrane segment 5 (TM5) in Na2 release and the conformational transition of neurotransmitter:sodium symporters toward the inward-open state.The Journal of biological chemistry · 2017Article
- Direct assessment of substrate binding to the Neurotransmitter:Sodium Symporter LeuT by solid state NMR.eLife · 2017Article
- The Environment Shapes the Inner Vestibule of LeuT.PLoS computational biology · 2016Article
- Transition metal ion FRET uncovers KNature communications · 2016Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Neurotransmitter:sodium symporters (NSSs) mediate reuptake of neurotransmitters from the synaptic cleft and are targets for several therapeutics and psychostimulants. The prokaryotic NSS homologue, LeuT, represents a principal structural model for Na(+)-coupled transport catalyzed by these proteins. Here, we used site-directed fluorescence quenching spectroscopy to identify in LeuT a substrate-induced conformational rearrangement at the inner gate conceivably leading to formation of a structural intermediate preceding transition to the inward-open conformation. The substrate-induced, Na(+)-dependent change required an intact primary substrate-binding site and involved increased water exposure of the cytoplasmic end of transmembrane segment 5. The findings were supported by simulations predicting disruption of an intracellular interaction network leading to a discrete rotation of transmembrane segment 5 and the adjacent intracellular loop 2. The magnitude of the spectroscopic response correlated inversely with the transport rate for different substrates, suggesting that stability of the intermediate represents an unrecognized rate-limiting barrier in the NSS transport mechanism.
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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.