Cryo-EM structures of excitatory amino acid transporter 3 visualize coupled substrate, sodium, and proton binding and transport.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
05
11
2020
accepted:
19
01
2021
entrez:
4
3
2021
pubmed:
5
3
2021
medline:
19
4
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33658209
pii: 7/10/eabf5814
doi: 10.1126/sciadv.abf5814
pmc: PMC7929514
pii:
doi:
Substances chimiques
Excitatory Amino Acid Transporter 3
0
Ions
0
Protons
0
SLC1A1 protein, human
0
Glutamic Acid
3KX376GY7L
Sodium
9NEZ333N27
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NINDS NIH HHS
ID : R01 NS064357
Pays : United States
Organisme : NINDS NIH HHS
ID : R37 NS085318
Pays : United States
Informations de copyright
Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
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