MS05-03 - Transport of Enantiomeric Neurotransmitters by SLC1A Family of Proteins

Albert Guskov (University of Groningen, Netherlands)

Mammalian glutamate transporters (belonging to Solute Carrier Family 1 of 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. We investigated binding and transport of enantiomeric substrates in archaeal homologue of glutamate transporters -  Glt_Tk from Thermococcus kodakarensis. We observed that Glt_Tktransports D-aspartate with identical Na⁺ : substrate coupling stoichiometry as L-aspartate, and that the affinities (K_d and K_m) for the two substrates are very similar. Additionally we solved a crystal structure of Glt_Tk with bound D-aspartate at 2.8 Å resolution and compared it with the L-aspartate bound Glt_Tk structure. The new structure explains how the geometrically different molecules L- and D-aspartate are recognized and transported by the protein in the same way and provides a clue to explain the puzzling observation why mammalian SLC1A transporters readily transport L- but not D-glutamate.