Allosteric gate modulation confers K⁺ coupling in glutamate transporters.

ABSTRACT: Excitatory amino acid transporters (EAATs) mediate glial and neuronal glutamate uptake to terminate synaptic transmission and to ensure low resting glutamate concentrations. Effective glutamate uptake is achieved by cotransport with 3 Na⁺ and 1 H⁺ , in exchange with 1 K⁺ . The underlying principles of this complex transport stoichiometry remain poorly understood. We use molecular dynamics simulations and electrophysiological experiments to elucidate how mammalian EAATs harness K⁺ gradients, unlike their K⁺ -independent prokaryotic homologues. Glutamate transport is achieved via elevator-like translocation of the transport domain. In EAATs, glutamate-free re-translocation is prevented by an external gate remaining open until K⁺

SUBMITTER: Kortzak D 

PROVIDER: S-EPMC6769379 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature