ArticleThe Journal of biological chemistry2010
Mechanism of cation binding to the glutamate transporter EAAC1 probed with mutation of the conserved amino acid residue Thr101.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 48 citations in OpenAlex.
- The ion-coupling mechanism of human excitatory amino acid transporters.The EMBO journal · 2022Article
- NaScience advances · 2020Article
- Mechanism and potential sites of potassium interaction with glutamate transporters.The Journal of general physiology · 2020Article
- Free-Energy Simulations Resolve the Low-Affinity NaBiophysical journal · 2019Article
- Article
- Both reentrant loops of the sodium-coupled glutamate transporters contain molecular determinants of cation selectivity.The Journal of biological chemistry · 2018Article
- Analysis of the quality of crystallographic data and the limitations of structural models.The Journal of general physiology · 2017Review
- Article
- Gating Charge Calculations by Computational Electrophysiology Simulations.Biophysical journal · 2017Article
- Mother-to-child transmission of HIV in Kenya: A cross-sectional analysis of the national database over nine years.PloS one · 2017Article
- Coupled binding mechanism of three sodium ions and aspartate in the glutamate transporter homologue GltNature communications · 2016Article
- SLC Transporters: Structure, Function, and Drug Discovery.MedChemComm · 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
- 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
- A Mutation in Transmembrane Domain 7 (TM7) of Excitatory Amino Acid Transporters Disrupts the Substrate-dependent Gating of the Intrinsic Anion Conductance and Drives the Channel into a Constitutively Open State.The Journal of biological chemistry · 2015Article
- Low Affinity and Slow Na+ Binding Precedes High Affinity Aspartate Binding in the Secondary-active Transporter GltPh.The Journal of biological chemistry · 2015Article
- Excitatory amino acid transporters: roles in glutamatergic neurotransmission.Neurochemistry international · 2014Review
- Na+ interactions with the neutral amino acid transporter ASCT1.The Journal of biological chemistry · 2014Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The glutamate transporter excitatory amino acid carrier 1 (EAAC1) catalyzes the co-transport of three Na(+) ions, one H(+) ion, and one glutamate molecule into the cell, in exchange for one K(+) ion. Na(+) binding to the glutamate-free form of the transporter generates a high affinity binding site for glutamate and is thus required for transport. Moreover, sodium binding to the transporters induces a basal anion conductance, which is further activated by glutamate. Here, we used the [Na(+)] dependence of this conductance as a read-out of Na(+) binding to the substrate-free transporter to study the impact of a highly conserved amino acid residue, Thr(101), in transmembrane domain 3. The apparent affinity of substrate-free EAAC1 for Na(+) was dramatically decreased by the T101A but not by the T101S mutation. Interestingly, in further contrast to EAAC1(WT), in the T101A mutant this [Na(+)] dependence was biphasic. This behavior can be explained by assuming that the binding of two Na(+) ions prior to glutamate binding is required to generate a high affinity substrate binding site. In contrast to the dramatic effect of the T101A mutation on Na(+) binding, other properties of the transporter, such as its ability to transport glutamate, were impaired but not eliminated. Our results are consistent with the existence of a cation binding site deeply buried in the membrane and involving interactions with the side chain oxygens of Thr(101) and Asp(367). A theoretical valence screening approach confirms that the predicted site of cation interaction has the potential to be a novel, so far undetected sodium binding site.
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