Speaker: Nicolás Reyes, PhD
Department of Physiology and Biophysics, Weill Medical
College Cornell University
New York - USA

Host

Dr. Manuel Palacín, IRB Barcelona

Wednesday, 17 February 2010, 13.30h Aula Fèlix Serratosa

Abstract

Glutamate is the most predominant neurotransmitter in the brain, but its extracellular concentration has to be kept low to prevent cell death and ensure normal neurotransmission. Integral plasma membrane proteins called glutamate transporters or excitatory amino acid transporters (EAATs), take up glutamate from the synaptic cleft into the cytoplasm of neurons and glia using the energy stored in the transmembrane ionic gradients. Thus, these enzymes couple the concentrative uptake of substrate to the transport of ions down their electrochemical gradients. Essential to this catalytic reaction is the isomerization of the transporters between outward- and inward-facing states, in which the substratebinding site is located in the extra- and intracellular side of the membrane, respectively. We have solved the crystal structure of a double-cysteine mutant of a prokaryotic glutamate transporter homolog, GLt_Ph, which is trapped in the inward-facing state by cysteine cross-linking. Together with the previously determined structures of Glt_Ph in the outward-facing state, we proposed a novel mechanism of transport for this homolog and its mammalian counterparts.

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