Binding and transport of D-aspartate by the glutamate transporter homologue GltTk
- University of Groningen, Netherlands
Abstract
Mammalian glutamate transporters are crucial players in neuronal communication as they perform neurotransmitter reuptake from the synaptic cleft. Besides L-glutamate and L-aspartate, they also recognize D-aspartate, which might participate in mammalian neurotransmission and/or neuromodulation. Much of the mechanistic insight in glutamate transport comes from studies of the archaeal homologues GltPh from Pyrococcus horikoshii and GltTk from Thermococcus kodakarensis. Here, we show that GltTk transports D-aspartate with identical Na+ : substrate coupling stoichiometry as L-aspartate, and that the affinities (Kd and Km) for the two substrates are similar. We determined a crystal structure of GltTk with bound D-aspartate at 2.8 Å resolution. Comparison of the L- and D-aspartate bound GltTk structures revealed that D-aspartate is accommodated with only minor rearrangements in the structure of the binding site. The structure explains how the geometrically different molecules L- and D-aspartate are recognized and transported by the protein in the same way.
Data availability
Diffraction data and the derived model have been deposited in PDB under the accession code 6R7R.
Article and author information
Author details
Funding
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (723014.002)
- Albert Guskov
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (865.11.001)
- Dirk Slotboom
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- José D Faraldo-Gómez, National Heart, Lung and Blood Institute, National Institutes of Health, United States
Version history
- Received: January 17, 2019
- Accepted: April 9, 2019
- Accepted Manuscript published: April 10, 2019 (version 1)
- Version of Record published: April 24, 2019 (version 2)
Copyright
© 2019, Arkhipova et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Binding and transport of D-aspartate by the glutamate transporter homologue GltTk
eLife 8:e45286.
https://doi.org/10.7554/eLife.45286
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