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

Arkhipova, V. I., Trinco, G., Thijs, E., Jensen, S., Slotboom, D. & Guskov, A., 1-May-2019, In : eLife. 8, e45286.

Research output: Contribution to journalArticleAcademicpeer-review

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.
Original languageEnglish
Article numbere45286
Publication statusPublished - 1-May-2019
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