Binding and transport of D-aspartate by the glutamate transporter homologue GltTk

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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 Glt_Ph from Pyrococcus horikoshii and Glt_Tkfrom Thermococcus kodakarensis. Here, we show that Glt_Tk transports D-aspartate with identical Na⁺: substrate coupling stoichiometry as L-aspartate, and that the affinities (K_d and K_m) for the two substrates are similar. We determined a crystal structure of Glt_Tk with bound D-aspartate at 2.8 Å resolution. Comparison of the L- and D-aspartate bound Glt_Tk 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.

The following data sets were generated

1. Arkhipova V
2. Trinco G
3. Ettema TW
4. Jensen S
5. Slotboom DJ
6. Guskov A
(2019) Diffraction data and the derived model
Protein Data Bank, 6R7R.

https://www.rcsb.org/

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Author details

Valentina Arkhipova

Groningen Biomolecular and Biotechnology Institute (GBB), University of Groningen, Groningen, Netherlands

Competing interests
The authors declare that no competing interests exist.
Gianluca Trinco

Groningen Biomolecular and Biotechnology Institute (GBB), University of Groningen, Groningen, Netherlands

Competing interests
The authors declare that no competing interests exist.
Thijs W Ettema

Groningen Biomolecular and Biotechnology Institute (GBB), University of Groningen, Groningen, Netherlands

Competing interests
The authors declare that no competing interests exist.
Sonja Jensen

Groningen Biomolecular and Biotechnology Institute (GBB), University of Groningen, Groningen, Netherlands

Competing interests
The authors declare that no competing interests exist.
Dirk Slotboom

Groningen Biomolecular and Biotechnology Institute (GBB), University of Groningen, Groningen, Netherlands

For correspondence
d.j.slotboom@rug.nl

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-5804-9689
Albert Guskov

Groningen Biomolecular and Biotechnology Institute (GBB), University of Groningen, Groningen, Netherlands

For correspondence
a.guskov@rug.nl

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-2340-2216

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.

Copyright

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.