1. Structural Biology and Molecular Biophysics

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

  1. Valentina Arkhipova
  2. Gianluca Trinco
  3. Thijs W Ettema
  4. Sonja Jensen
  5. Dirk Slotboom  Is a corresponding author
  6. Albert Guskov  Is a corresponding author
  1. University of Groningen, Netherlands
https://doi.org/10.7554/eLife.45286
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Cite this article
  1. Valentina Arkhipova
  2. Gianluca Trinco
  3. Thijs W Ettema
  4. Sonja Jensen
  5. Dirk Slotboom
  6. Albert Guskov
(2019)
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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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.

The following data sets were generated

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Author details

  1. Valentina Arkhipova

    Groningen Biomolecular and Biotechnology Institute (GBB), University of Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.

  2. Gianluca Trinco

    Groningen Biomolecular and Biotechnology Institute (GBB), University of Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.

  3. Thijs W Ettema

    Groningen Biomolecular and Biotechnology Institute (GBB), University of Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.

  4. Sonja Jensen

    Groningen Biomolecular and Biotechnology Institute (GBB), University of Groningen, Groningen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.

  5. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5804-9689

  6. 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.
    ORCID icon "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

© 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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  1. Valentina Arkhipova
  2. Gianluca Trinco
  3. Thijs W Ettema
  4. Sonja Jensen
  5. Dirk Slotboom
  6. Albert Guskov
(2019)
Binding and transport of D-aspartate by the glutamate transporter homologue GltTk
eLife 8:e45286.
https://doi.org/10.7554/eLife.45286

Share this article

https://doi.org/10.7554/eLife.45286

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