Crystal structures of an archaeal homologue of mammalian glutamate transporters in apo and ion-only bound outward- and inward-facing states reveal ion-coupled conformational changes supporting mechanisms of coupling, gating, and transport.
Substrate releasing or inhibitor binding on the intracellular side of a glutamate transporter homologue require movements of the transport domain through the lipid membrane, which undergoes adaptive deformations.
Cryo-EM structures of unliganded SLC1A5 and its complex with glutamine in outward-facing state provide insights into the substrate specificity and transport mechanism and will be helpful for developing selective inhibitors.
In mammals, the vesicular glutamate transporter 1 acquired a proline-rich sequence that negatively regulates the spontaneous release of glutamate by reducing the exchange of synaptic vesicles along the axon.
Novel evidence on the molecular determinants of the dual function, anion permeation and substrate transport, of excitatory amino acid transporters opens avenues toward illuminating how these transporters regulate synaptic function and contribute to neurological conditions.
Sodium ions control the rates of both substrate binding and dissociation of an archaeal homologue of glutamate transporters in a manner that minimizes binding intermediates and maximizes transport efficiency.