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

Valentina Ivanovna Arkhipova, Gianluca Trinco, Ettema Thijs, Sonja Jensen, Dirk Slotboom*, Albert Guskov

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

19 Citaten (Scopus)
328 Downloads (Pure)


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.
Originele taal-2English
Aantal pagina's12
StatusPublished - 1-mei-2019

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