6X2Z

hEAAT3-OFS-Asp

Summary for 6X2Z

• Entry DOI: 10.2210/pdb6x2z/pdb
• EMDB information: 22014
• Descriptor: Excitatory amino acid transporter 3, ASPARTIC ACID, SODIUM ION (3 entities in total)
• Functional Keywords: heaat3 outward-facing, full-bound, transport protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 57477.24

Authors

Qiu, B.,Matthies, D.,Boudker, O. (deposition date: 2020-05-21, release date: 2021-03-17, Last modification date: 2024-03-06)

Primary citation

Qiu, B.,Matthies, D.,Fortea, E.,Yu, Z.,Boudker, O.
Cryo-EM structures of excitatory amino acid transporter 3 visualize coupled substrate, sodium, and proton binding and transport.
Sci Adv, 7:-, 2021

PubMed 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.

PubMed: 33658209
DOI: 10.1126/sciadv.abf5814

Experimental method

ELECTRON MICROSCOPY (3.03 Å)