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Binding and transport of D-aspartate by the glutamate transporter homolog Glt(Tk)

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...

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Detalles Bibliográficos
Autores principales: Arkhipova, Valentina, Trinco, Gianluca, Ettema, Thijs W, Jensen, Sonja, Slotboom, Dirk J, Guskov, Albert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6482001/
https://www.ncbi.nlm.nih.gov/pubmed/30969168
http://dx.doi.org/10.7554/eLife.45286
Descripción
Sumario: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 Glt(Ph) from Pyrococcus horikoshii and Glt(Tk) from Thermococcus kodakarensis. Here, we show that Glt(Tk) transports 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 similar. We determined a crystal structure of Glt(Tk) with bound D-aspartate at 2.8 Å resolution. Comparison of the L- and D-aspartate bound Glt(Tk) 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.