ArticleBiophysical journal2014
Molecular dynamics simulations elucidate the mechanism of proton transport in the glutamate transporter EAAT3.
Article in Biophysical journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 13 citations in OpenAlex.
- The Transporter-Mediated Cellular Uptake and Efflux of Pharmaceutical Drugs and Biotechnology Products: How and Why Phospholipid Bilayer Transport Is Negligible in Real Biomembranes.Molecules (Basel, Switzerland) · 2021Review
- Cryo-EM structures of excitatory amino acid transporter 3 visualize coupled substrate, sodium, and proton binding and transport.Science advances · 2021Article
- Mechanism and potential sites of potassium interaction with glutamate transporters.The Journal of general physiology · 2020Article
- A KThe Journal of biological chemistry · 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
- Substrate transport and anion permeation proceed through distinct pathways in glutamate transporters.eLife · 2017Article
- Computational Studies of Glutamate Transporters.Biomolecules · 2015Review
- Computational characterization of structural dynamics underlying function in active membrane transporters.Current opinion in structural biology · 2015Review
- Coupling between neurotransmitter translocation and protonation state of a titratable residue during Na ⁺-coupled transport.Biophysical journal · 2014Article
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2 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
The uptake of glutamate in nerve synapses is carried out by the excitatory amino acid transporters (EAATs), involving the cotransport of a proton and three Na(+) ions and the countertransport of a K(+) ion. In this study, we use an EAAT3 homology model to calculate the pKa of several titratable residues around the glutamate binding site to locate the proton carrier site involved in the translocation of the substrate. After identifying E374 as the main candidate for carrying the proton, we calculate the protonation state of this residue in different conformations of EAAT3 and with different ligands bound. We find that E374 is protonated in the fully bound state, but removing the Na2 ion and the substrate reduces the pKa of this residue and favors the release of the proton to solution. Removing the remaining Na(+) ions again favors the protonation of E374 in both the outward- and inward-facing states, hence the proton is not released in the empty transporter. By calculating the pKa of E374 with a K(+) ion bound in three possible sites, we show that binding of the K(+) ion is necessary for the release of the proton in the inward-facing state. This suggests a mechanism in which a K(+) ion replaces one of the ligands bound to the transporter, which may explain the faster transport rates of the EAATs compared to its archaeal homologs.
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