ArticleBiochemistry2007
Two conformational changes are associated with glutamate translocation by the glutamate transporter EAAC1.
Article in Biochemistry, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- The high-energy transition state of the glutamate transporter homologue GltPh.The EMBO journal · 2021Article
- Pre-steady-state Kinetic Analysis of Amino Acid Transporter SLC6A14 Reveals Rapid Turnover Rate and Substrate Translocation.Frontiers in physiology · 2021Article
- Electrogenic Steps Associated with Substrate Binding to the Neuronal Glutamate Transporter EAAC1.The Journal of biological chemistry · 2016Article
- Molecular dynamics simulations elucidate the mechanism of proton transport in the glutamate transporter EAAT3.Biophysical journal · 2014Article
- SLC1 glutamate transporters.Pflugers Archiv : European journal of physiology · 2014Review
- Mechanism of transport modulation by an extracellular loop in an archaeal excitatory amino acid transporter (EAAT) homolog.The Journal of biological chemistry · 2013Article
- Induced fit substrate binding to an archeal glutamate transporter homologue.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Voltage-dependent processes in the electroneutral amino acid exchanger ASCT2.The Journal of general physiology · 2013Article
- Charge compensation mechanism of a Na+-coupled, secondary active glutamate transporter.The Journal of biological chemistry · 2012Article
- Mechanism of inhibition of the glutamate transporter EAAC1 by the conformationally constrained glutamate analogue (+)-HIP-B.Biochemistry · 2012Article
- The discovery of slowness: low-capacity transport and slow anion channel gating by the glutamate transporter EAAT5.Biophysical journal · 2011Article
- Hetero-oligomerization of neuronal glutamate transporters.The Journal of biological chemistry · 2011Article
- New views of glutamate transporter structure and function: advances and challenges.Neuropharmacology · 2011Review
- Capturing Functional Motions of Membrane Channels and Transporters with Molecular Dynamics Simulation.Journal of computational and theoretical nanoscience · 2010Article
- Identification of the third Na+ site and the sequence of extracellular binding events in the glutamate transporter.Biophysical journal · 2010Article
- Mechanism of cation binding to the glutamate transporter EAAC1 probed with mutation of the conserved amino acid residue Thr101.The Journal of biological chemistry · 2010Article
- Inward-facing conformation of glutamate transporters as revealed by their inverted-topology structural repeats.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Molecular simulations elucidate the substrate translocation pathway in a glutamate transporter.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Dynamics of the extracellular gate and ion-substrate coupling in the glutamate transporter.Biophysical journal · 2008Article
- Glutamate forward and reverse transport: from molecular mechanism to transporter-mediated release after ischemia.IUBMB life · 2008Review
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Glutamate is transported across membranes by means of a carrier mechanism that is thought to require conformational changes of the transport protein. In this work, we have determined the thermodynamic parameters of glutamate and the Na+ binding steps to their extracellular binding sites along with the activation parameters of rapid, glutamate-induced processes in the transport cycle by analyzing the temperature dependence of glutamate transport at steady state and pre-steady state. Our results suggest that glutamate binding to the transporter is driven by a negative reaction enthalpy (DeltaH0 = -33 kJ/mol), whereas the tighter binding of the non-transportable inhibitor TBOA is caused by an additional increase in entropy. Processes linked to the binding of glutamate and Na+ to the transporter are associated with low activation barriers, indicative of diffusion-controlled reactions. The activation enthalpies of two processes in the glutamate translocation branch of the transport cycle were DeltaH++ = 95 kJ/mol and DeltaH++ = 120 kJ/mol, respectively. Such large values of DeltaH++ suggest that these processes are rate-limited by conformational changes of the transporter. We also found a large activation barrier for steady-state glutamate transport, which is rate-limited by the K+-dependent relocation of the empty transporter. Together, these results suggest that two conformational changes accompany glutamate translocation and at least one conformational change accompanies the relocation of the empty transporter. We interpret the data with an alternating access model that includes the closing and opening of an extracellular and an intracellular gate, respectively, in analogy to a hypothetical model proposed previously on the basis of the crystal structure of the bacterial glutamate transporter GltPh.
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