ArticleProceedings of the National Academy of Sciences of the United States of America2013
Induced fit substrate binding to an archeal glutamate transporter homologue.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32 citing papers in PubMed, 54 citations in OpenAlex.
- Evolutionary analysis reveals the origin of sodium coupling in glutamate transporters.Nature structural & molecular biology · 2025Article
- Allosteric modulation of proton binding confers Cl- activation and glutamate selectivity to vesicular glutamate transporters.PLoS computational biology · 2025Article
- Article
- 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
- The ion-coupling mechanism of human excitatory amino acid transporters.The EMBO journal · 2022Article
- Molecular Basis of Coupled Transport and Anion Conduction in Excitatory Amino Acid Transporters.Neurochemical research · 2022Review
- On the Role of a Conserved Methionine in the NaNeurochemical research · 2022Article
- 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
- Kinetic mechanism of NaCommunications biology · 2021Article
- Observing spontaneous, accelerated substrate binding in molecular dynamics simulations of glutamate transporters.PloS one · 2021Article
- Mechanisms of ligand binding.Biophysics reviews · 2020Review
- NaScience advances · 2020Article
- Elevator-type mechanisms of membrane transport.Biochemical Society transactions · 2020Review
- Allosteric gate modulation confers KThe EMBO journal · 2019Article
- Free-Energy Simulations Resolve the Low-Affinity NaBiophysical journal · 2019Article
- Investigation of the allosteric coupling mechanism in a glutamate transporter homolog via unnatural amino acid mutagenesis.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Article
- Article
- Both reentrant loops of the sodium-coupled glutamate transporters contain molecular determinants of cation selectivity.The Journal of biological chemistry · 2018Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Excitatory amino acid transporters (EAATs) are a class of glutamate transporters that terminate glutamatergic synaptic transmission in the mammalian CNS. GltPh, an archeal EAAT homolog from Pyrococcus horikoshii, is currently the only member with a known 3D structure. Here, we studied the kinetics of substrate binding of a single tryptophan mutant (L130W) GltPh in detergent micelles. At low millimolar [Na(+)], the addition of L-aspartate resulted in complex time courses of W130 fluorescence changes over tens of seconds. With increasing [Na(+)], the kinetics were dominated by a fast component [k(obs,fast); K(D) (Na(+)) = 22 ± 3 mM, n(Hill )= 1.7 ± 0.3] with values of k(obs,fast) rising in a saturable manner to ≈ 500 s(-1) (at 6 °C) with increasing [L-aspartate]. The binding kinetics of L-aspartate differed from the binding kinetics of two alternative substrates: L-cysteine sulfinic acid and d-aspartate. L-cysteine sulfinic acid bound with higher affinity than L-aspartate but involved lower saturating rates, whereas the saturating rates after D-aspartate binding were higher. Thus, after the association of two Na(+) to the empty transporter, GltPh binds amino acids by induced fit. Cross-linking and proteolysis experiments suggest that the induced fit results from the closure of helical hairpin 2. This conformational change is faster for GltPh than for most mammalian homologues, whereas the amino acid association rates are similar. Our data reveal the importance of induced fit for substrate selection in EAATs and illustrate how high-affinity binding and the efficient transport of glutamate can be accomplished simultaneously by this class of transporters.
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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.