Large domain movements through the lipid bilayer mediate substrate release and inhibition of glutamate transporters.

ABSTRACT: Glutamate transporters are essential players in glutamatergic neurotransmission in the brain, where they maintain extracellular glutamate below cytotoxic levels and allow for rounds of transmission. The structural bases of their function are well established, particularly within a model archaeal homolog, sodium, and aspartate symporter Glt_Ph. However, the mechanism of gating on the cytoplasmic side of the membrane remains ambiguous. We report Cryo-EM structures of Glt_Ph reconstituted into nanodiscs, including those structurally constrained in the cytoplasm-facing state and either apo, bound to sodium ions only, substrate, or blockers. The structures show that both substrate translocation and release involve movements of the bulky transport domain through the lipid bil

SUBMITTER: Wang X 

PROVIDER: S-EPMC7682989 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature