The ion-coupling mechanism of human excitatory amino acid transporters.

ABSTRACT: Excitatory amino acid transporters (EAATs) maintain glutamate gradients in the brain essential for neurotransmission and to prevent neuronal death. They use ionic gradients as energy source and co-transport transmitter into the cytoplasm with Na⁺ and H⁺ , while counter-transporting K⁺ to re-initiate the transport cycle. However, the molecular mechanisms underlying ion-coupled transport remain incompletely understood. Here, we present 3D X-ray crystallographic and cryo-EM structures, as well as thermodynamic analysis of human EAAT1 in different ion bound conformations, including elusive counter-transport ion bound states. Binding energies of Na⁺ and H⁺ , and unexpectedly Ca²⁺ , are coupled to neurotransmitter binding. Ca

SUBMITTER: Canul-Tec JC 

PROVIDER: S-EPMC8724772 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature