Na⁺-dependent gate dynamics and electrostatic attraction ensure substrate coupling in glutamate transporters.

ABSTRACT: Excitatory amino acid transporters (EAATs) harness [Na⁺], [K⁺], and [H⁺] gradients for fast and efficient glutamate removal from the synaptic cleft. Since each glutamate is cotransported with three Na⁺ ions, [Na⁺] gradients are the predominant driving force for glutamate uptake. We combined all-atom molecular dynamics simulations, fluorescence spectroscopy, and x-ray crystallography to study Na⁺:substrate coupling in the EAAT homolog Glt_Ph A lipidic cubic phase x-ray crystal structure of wild-type, Na⁺-only bound Glt_Ph at 2.5-Å resolution revealed the fully open, outward-facing state primed for subsequent substrate binding. Simulations and kinetic experiments established that only the binding

SUBMITTER: Alleva C 

PROVIDER: S-EPMC7673805 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature