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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

12 Citations (Scopus)
265 Downloads (Pure)

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.
Original languageEnglish
Article numbere45286
Number of pages12
JournaleLife
Volume8
DOIs
Publication statusPublished - 1-May-2019

Keywords

  • AMINO-ACID
  • CRYSTAL-STRUCTURE
  • STRUCTURAL BASIS
  • SUBSTRATE
  • STOICHIOMETRY
  • RECOGNITION
  • FEATURES
  • INHIBITION
  • REFINEMENT
  • MECHANISMS

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