ArticleThe Journal of biological chemistry2006
Neutralization of the aspartic acid residue Asp-367, but not Asp-454, inhibits binding of Na+ to the glutamate-free form and cycling of the glutamate transporter EAAC1.
Article in The Journal of biological chemistry, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 76 citations in OpenAlex.
- Evolutionary analysis reveals the origin of sodium coupling in glutamate transporters.Nature structural & molecular biology · 2025Article
- 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
- Structural basis of the obligatory exchange mode of human neutral amino acid transporter ASCT2.Nature communications · 2024Article
- Structural basis of ligand binding modes of human EAAT2.Nature communications · 2022Article
- Functional and Kinetic Comparison of Alanine Cysteine Serine Transporters ASCT1 and ASCT2.Biomolecules · 2022Article
- On the Role of a Conserved Methionine in the NaNeurochemical research · 2022Article
- Cryo-EM structures of excitatory amino acid transporter 3 visualize coupled substrate, sodium, and proton binding and transport.Science advances · 2021Article
- Pre-steady-state Kinetic Analysis of Amino Acid Transporter SLC6A14 Reveals Rapid Turnover Rate and Substrate Translocation.Frontiers in physiology · 2021Article
- Article
- Cellular Physiology and Pathophysiology of EAAT Anion Channels.Frontiers in cellular neuroscience · 2021Review
- Observing spontaneous, accelerated substrate binding in molecular dynamics simulations of glutamate transporters.PloS one · 2021Article
- Mechanism and potential sites of potassium interaction with glutamate transporters.The Journal of general physiology · 2020Article
- Allosteric gate modulation confers KThe EMBO journal · 2019Article
- A KThe Journal of biological chemistry · 2019Article
- Rare SLC1A1 variants in hot water epilepsy.Human genetics · 2017Article
- Coupled binding mechanism of three sodium ions and aspartate in the glutamate transporter homologue GltNature communications · 2016Article
- 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
- The Hydroxyl Side Chain of a Highly Conserved Serine Residue Is Required for Cation Selectivity and Substrate Transport in the Glial Glutamate Transporter GLT-1/SLC1A2.The Journal of biological chemistry · 2015Article
- Computational Studies of Glutamate Transporters.Biomolecules · 2015Review
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3 authors at 1 institution in 1 country.
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Abstract
Substrate transport by the plasma membrane glutamate transporter EAAC1 is coupled to cotransport of three sodium ions. One of these Na(+) ions binds to the transporter already in the absence of glutamate. Here, we have investigated the possible involvement of two conserved aspartic acid residues in transmembrane segments 7 and 8 of EAAC1, Asp-367 and Asp-454, in Na(+) cotransport. To test the effect of charge neutralization mutations in these positions on Na(+) binding to the glutamate-free transporter, we recorded the Na(+)-induced anion leak current to determine the K(m) of EAAC1 for Na(+). For EAAC1(WT), this K(m) was determined as 120 mm. When the negative charge of Asp-367 was neutralized by mutagenesis to asparagine, Na(+) activated the anion leak current with a K(m) of about 2 m, indicating dramatically impaired Na(+) binding to the mutant transporter. In contrast, the Na(+) affinity of EAAC1(D454N) was virtually unchanged compared with the wild type transporter (K(m) = 90 mm). The reduced occupancy of the Na(+) binding site of EAAC1(D367N) resulted in a dramatic reduction in glutamate affinity (K(m) = 3.6 mm, 140 mm [Na(+)]), which could be partially overcome by increasing extracellular [Na(+)]. In addition to impairing Na(+) binding, the D367N mutation slowed glutamate transport, as shown by pre-steady-state kinetic analysis of transport currents, by strongly decreasing the rate of a reaction step associated with glutamate translocation. Our data are consistent with a model in which Asp-367, but not Asp-454, is involved in coordinating the bound Na(+) in the glutamate-free transporter form.
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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.