Binding and transport of D-aspartate by the glutamate transporter homolog GltTk
Valentina Arkhipova,
Gianluca Trinco,
Thijs W Ettema,
Sonja Jensen,
Dirk J Slotboom,
Albert Guskov
Affiliations
Valentina Arkhipova
Groningen Biomolecular Sciences and Biotechnology Institute, Zernike Institute for Advanced Materials, University of Groningen, Groningen, The Netherlands
Gianluca Trinco
Groningen Biomolecular Sciences and Biotechnology Institute, Zernike Institute for Advanced Materials, University of Groningen, Groningen, The Netherlands
Thijs W Ettema
Groningen Biomolecular Sciences and Biotechnology Institute, Zernike Institute for Advanced Materials, University of Groningen, Groningen, The Netherlands
Sonja Jensen
Groningen Biomolecular Sciences and Biotechnology Institute, Zernike Institute for Advanced Materials, University of Groningen, Groningen, The Netherlands
Groningen Biomolecular Sciences and Biotechnology Institute, Zernike Institute for Advanced Materials, University of Groningen, Groningen, The Netherlands
Groningen Biomolecular Sciences and Biotechnology Institute, Zernike Institute for Advanced Materials, University of Groningen, Groningen, The Netherlands
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 archeal homologs 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.
