Cryo-EM structures of excitatory amino acid transporter 3 visualize coupled substrate, sodium, and proton binding and transport.

janelia7_blocks-janelia7_biblio_header | block

Sciences Advances. 2021 Mar 03;7(10). doi: 10.1126/sciadv.abf5814

Qiu B, Matthies D, Fortea E, Yu Z, Boudker O

janelia7_blocks-janelia7_biblio_abstract | block

Abstract

Human excitatory amino acid transporter 3 (hEAAT3) mediates glutamate uptake in neurons, intestine, and kidney. Here, we report cryo-EM structures of hEAAT3 in several functional states where the transporter is empty, bound to coupled sodium ions only, or fully loaded with three sodium ions, a proton, and the substrate aspartate. The structures suggest that hEAAT3 operates by an elevator mechanism involving three functionally independent subunits. When the substrate-binding site is near the cytoplasm, it has a remarkably low affinity for the substrate, perhaps facilitating its release and allowing the rapid transport turnover. The mechanism of the coupled uptake of the sodium ions and the substrate is conserved across evolutionarily distant families and is augmented by coupling to protons in EAATs. The structures further suggest a mechanism by which a conserved glutamate residue mediates proton symport.

PMID: 33658209 [PubMed - indexed for MEDLINE]

node:body | entity_field

Main Menu (Mobile)- Block

Main Menu - Block

Cryo-EM structures of excitatory amino acid transporter 3 visualize coupled substrate, sodium, and proton binding and transport.

Abstract

PMID: 33658209 [PubMed - indexed for MEDLINE]

Janelia Authors