ArticleThe Journal of general physiology2013
Voltage-dependent processes in the electroneutral amino acid exchanger ASCT2.
Article in The Journal of general physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Structural basis of the obligatory exchange mode of human neutral amino acid transporter ASCT2.Nature communications · 2024Article
- Article
- Do Amino Acid Antiporters Have Asymmetric Substrate Specificity?Biomolecules · 2023Article
- Article
- Alanine serine cysteine transporter (ASCT) substrate binding site properties probed with hydroxyhomoserine esters.Journal of physical organic chemistry · 2022Article
- Characterizing unexpected interactions of a glutamine transporter inhibitor with members of the SLC1A transporter family.The Journal of biological chemistry · 2022Article
- Functional and Kinetic Comparison of Alanine Cysteine Serine Transporters ASCT1 and ASCT2.Biomolecules · 2022Article
- Rational design of ASCT2 inhibitors using an integrated experimental-computational approach.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- A structural view onto disease-linked mutations in the human neutral amino acid exchanger ASCT1.Computational and structural biotechnology journal · 2021Article
- Interaction of the neutral amino acid transporter ASCT2 with basic amino acids.The Biochemical journal · 2020Article
- The Human SLC1A5 Neutral Amino Acid Transporter Catalyzes a pH-Dependent Glutamate/Glutamine Antiport, as Well.Frontiers in cell and developmental biology · 2020Article
- Novel alanine serine cysteine transporter 2 (ASCT2) inhibitors based on sulfonamide and sulfonic acid ester scaffolds.The Journal of general physiology · 2019Article
- Determining the molecular basis of voltage sensitivity in membrane proteins.The Journal of general physiology · 2018Article
- Cryo-EM structure of the human neutral amino acid transporter ASCT2.Nature structural & molecular biology · 2018Article
- Cys Site-Directed Mutagenesis of the Human SLC1A5 (ASCT2) Transporter: Structure/Function Relationships and Crucial Role of Cys467 for Redox Sensing and Glutamine Transport.International journal of molecular sciences · 2018Article
- Structural characterisation reveals insights into substrate recognition by the glutamine transporter ASCT2/SLC1A5.Nature communications · 2018Article
- The Human SLC1A5 (ASCT2) Amino Acid Transporter: From Function to Structure and Role in Cell Biology.Frontiers in cell and developmental biology · 2018Review
- Structure activity relationships of benzylproline-derived inhibitors of the glutamine transporter ASCT2.Bioorganic & medicinal chemistry letters · 2017Article
- Computational Studies of Glutamate Transporters.Biomolecules · 2015Review
- Ligand Discovery for the Alanine-Serine-Cysteine Transporter (ASCT2, SLC1A5) from Homology Modeling and Virtual Screening.PLoS computational biology · 2015Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Neutral amino acid exchange by the alanine serine cysteine transporter (ASCT)2 was reported to be electroneutral and coupled to the cotransport of one Na(+) ion. The cotransported sodium ion carries positive charge. Therefore, it is possible that amino acid exchange is voltage dependent. However, little information is available on the electrical properties of the ASCT2 amino acid transport process. Here, we have used a combination of experimental and computational approaches to determine the details of the amino acid exchange mechanism of ASCT2. The [Na(+)] dependence of ASCT2-associated currents indicates that the Na(+)/amino acid stoichiometry is at least 2:1, with at least one sodium ion binding to the amino acid-free apo form of the transporter. When the substrate and two Na(+) ions are bound, the valence of the transport domain is +0.81. Consistently, voltage steps applied to ASCT2 in the fully loaded configuration elicit transient currents that decay on a millisecond time scale. Alanine concentration jumps at the extracellular side of the membrane are followed by inwardly directed transient currents, indicative of translocation of net positive charge during exchange. Molecular dynamics simulations are consistent with these results and point to a sequential binding process in which one or two modulatory Na(+) ions bind with high affinity to the empty transporter, followed by binding of the amino acid substrate and the subsequent binding of a final Na(+) ion. Overall, our results are consistent with voltage-dependent amino acid exchange occurring on a millisecond time scale, the kinetics of which we predict with simulations. Despite some differences, transport mechanism and interaction with Na(+) appear to be highly conserved between ASCT2 and the other members of the solute carrier 1 family, which transport acidic amino acids.
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