ArticleBiophysical journal2008
Dynamics of the extracellular gate and ion-substrate coupling in the glutamate transporter.
Article in Biophysical journal, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 80 citations in OpenAlex.
- Conformational free energy landscape of a glutamate transporter and microscopic details of its transport mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Structural basis of the obligatory exchange mode of human neutral amino acid transporter ASCT2.Nature communications · 2024Article
- Microscopic Characterization of the Chloride Permeation Pathway in the Human Excitatory Amino Acid Transporter 1 (EAAT1).ACS chemical neuroscience · 2022Article
- Linking function to global and local dynamics in an elevator-type transporter.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The high-energy transition state of the glutamate transporter homologue GltPh.The EMBO journal · 2021Article
- Observing spontaneous, accelerated substrate binding in molecular dynamics simulations of glutamate transporters.PloS one · 2021Article
- Structural ensemble of a glutamate transporter homologue in lipid nanodisc environment.Nature communications · 2020Article
- Advances and Challenges in Rational Drug Design for SLCs.Trends in pharmacological sciences · 2019Review
- Free-Energy Simulations Resolve the Low-Affinity NaBiophysical journal · 2019Article
- Investigation of the allosteric coupling mechanism in a glutamate transporter homolog via unnatural amino acid mutagenesis.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Analysis of the quality of crystallographic data and the limitations of structural models.The Journal of general physiology · 2017Review
- Substrate transport and anion permeation proceed through distinct pathways in glutamate transporters.eLife · 2017Article
- TM4 of the glutamate transporter GLT-1 experiences substrate-induced motion during the transport cycle.Scientific reports · 2016Article
- Transport mechanism of a glutamate transporter homologue GltPh.Biochemical Society transactions · 2016Review
- Electrogenic Steps Associated with Substrate Binding to the Neuronal Glutamate Transporter EAAC1.The Journal of biological chemistry · 2016Article
- Molecular physiology of EAAT anion channels.Pflugers Archiv : European journal of physiology · 2016Review
- Microscopic Characterization of Membrane Transporter Function by In Silico Modeling and Simulation.Methods in enzymology · 2016Review
- Computational Studies of Glutamate Transporters.Biomolecules · 2015Review
- Refinement of the Central Steps of Substrate Transport by the Aspartate Transporter GltPh: Elucidating the Role of the Na2 Sodium Binding Site.PLoS computational biology · 2015Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Glutamate transporters (GluTs) are the primary regulators of extracellular concentration of the neurotransmitter glutamate in the central nervous system. In this study, we have investigated the dynamics and coupling of the substrate and Na(+) binding sites, and the mechanism of cotransport of Na(+) ions, using molecular dynamics simulations of a membrane-embedded model of GluT in its apo (empty form) and various Na(+)- and/or substrate-bound states. The results shed light on the mechanism of the extracellular gate and on the sequence of binding of the substrate and Na(+) ions to GluT during the transport cycle. The results suggest that the helical hairpin HP2 plays the key role of the extracellular gate for the substrate binding site, and that the opening and closure of the gate is controlled by substrate binding. GluT adopts an open conformation in the absence of the substrate exposing the binding sites of the substrate and Na(+) ions to the extracellular solution. Based on the calculated trajectories, we propose that Na1 is the first element to bind GluT, as it is found to be important for the completion of the substrate binding site. The subsequent binding of the substrate, in turn, is shown to result in an almost complete closure of the extracellular gate and the formation of the Na2 binding site. Finally, binding of Na2 locks the extracellular gate and completes the formation of the occluded state of GluT.
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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.