Structural ensemble of a glutamate transporter homologue in lipid nanodisc environment

Nat Commun. 2020 Feb 21;11(1):998. doi: 10.1038/s41467-020-14834-8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport System X-AG / chemistry*
  • Amino Acid Transport System X-AG / genetics
  • Amino Acid Transport System X-AG / metabolism
  • Archaeal Proteins / chemistry*
  • Archaeal Proteins / genetics
  • Archaeal Proteins / metabolism
  • Aspartic Acid / metabolism
  • Binding Sites
  • Cryoelectron Microscopy
  • Lipids / chemistry
  • Models, Molecular
  • Nanostructures / chemistry
  • Protein Conformation
  • Protein Structure, Quaternary
  • Pyrococcus horikoshii / metabolism
  • Single Molecule Imaging
  • Symporters / chemistry
  • Symporters / metabolism
  • Thermococcus / genetics
  • Thermococcus / metabolism


  • Amino Acid Transport System X-AG
  • Archaeal Proteins
  • Lipids
  • Symporters
  • Aspartic Acid