ArticleThe Journal of biological chemistry2015
Low Affinity and Slow Na+ Binding Precedes High Affinity Aspartate Binding in the Secondary-active Transporter GltPh.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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34 citing papers in PubMed, 46 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
- Mutation in glutamate transporter homologue GltTk provides insights into pathologic mechanism of episodic ataxia 6.Nature communications · 2023Article
- Distinct roles of the NaProceedings of the National Academy of Sciences of the United States of America · 2022Article
- The archaeal glutamate transporter homologue GltPh shows heterogeneous substrate binding.The Journal of general physiology · 2022Article
- High-speed atomic force microscopy reveals a three-state elevator mechanism in the citrate transporter CitS.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- On the Role of a Conserved Methionine in the NaNeurochemical research · 2022Article
- Molecular Basis of Coupled Transport and Anion Conduction in Excitatory Amino Acid Transporters.Neurochemical research · 2022Review
- 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
- Thermostability-based binding assays reveal complex interplay of cation, substrate and lipid binding in the bacterial DASS transporter, VcINDY.The Biochemical journal · 2021Article
- Kinetic mechanism of NaCommunications biology · 2021Article
- Toward a Molecular Basis of Cellular Nucleoside Transport in Humans.Chemical reviews · 2021Review
- 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
- Solvent accessibility changes in a NaThe Journal of biological chemistry · 2020Article
- Article
- NaScience advances · 2020Article
- Saturation transfer difference NMR on the integral trimeric membrane transport protein GltPh determines cooperative substrate binding.Scientific reports · 2020Article
- Elevator-type mechanisms of membrane transport.Biochemical Society transactions · 2020Review
- Structural ensemble of a glutamate transporter homologue in lipid nanodisc environment.Nature communications · 2020Article
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4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GltPh from Pyrococcus horikoshii is a homotrimeric Na(+)-coupled aspartate transporter. It belongs to the widespread family of glutamate transporters, which also includes the mammalian excitatory amino acid transporters that take up the neurotransmitter glutamate. Each protomer in GltPh consists of a trimerization domain involved in subunit interactions and a transport domain containing the substrate binding site. Here, we have studied the dynamics of Na(+) and aspartate binding to GltPh. Tryptophan fluorescence measurements on the fully active single tryptophan mutant F273W revealed that Na(+) binds with low affinity to the apoprotein (Kd 120 mm), with a particularly low kon value (5.1 m(-1)s(-1)). At least two sodium ions bind before aspartate. The binding of Na(+) requires a very high activation energy (Ea 106.8 kJ mol(-1)) and consequently has a large Q10 value of 4.5, indicative of substantial conformational changes before or after the initial binding event. The apparent affinity for aspartate binding depended on the Na(+) concentration present. Binding of aspartate was not observed in the absence of Na(+), whereas in the presence of high Na(+) concentrations (above the Kd for Na(+)) the dissociation constants for aspartate were in the nanomolar range, and the aspartate binding was fast (kon of 1.4 × 10(5) m(-1)s(-1)), with low Ea and Q10 values (42.6 kJ mol(-1) and 1.8, respectively). We conclude that Na(+) binding is most likely the rate-limiting step for substrate binding.
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