Structural ensemble of a glutamate transporter homologue in lipid nanodisc environment

Valentina Arkhipova, Albert Guskov*, Dirk Slotboom

*Corresponding author voor dit werk

OnderzoeksoutputAcademicpeer review

48 Citaten (Scopus)
178 Downloads (Pure)

Samenvatting

Glutamate transporters are cation-coupled secondary active membrane transporters that clear the neurotransmitter L-glutamate from the synaptic cleft. These transporters are homotrimers, with each protomer functioning independently by an elevator-type mechanism, in which a mobile transport domain alternates between inward- and outward-oriented states. Using single-particle cryo-EM we have determined five structures of the glutamate transporter homologue GltTk, a Na+- L-aspartate symporter, embedded in lipid nanodiscs. Dependent on the substrate concentrations used, the protomers of the trimer adopt a variety of asymmetrical conformations, consistent with the independent movement. Six of the 15 resolved protomers are in a hitherto elusive state of the transport cycle in which the inward-facing transporters are loaded with Na+ ions. These structures explain how substrate-leakage is prevented – a strict requirement for coupled transport. The belt protein of the lipid nanodiscs bends around the inward oriented protomers, suggesting that membrane deformations occur during transport.
Originele taal-2English
Artikelnummer998
Aantal pagina's9
TijdschriftNature Communications
Volume11
Nummer van het tijdschrift1
DOI's
StatusPublished - 21-feb.-2020

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