8CTD

Human excitatory amino acid transporter 3 (EAAT3) protomer with bound glutamate in an outward facing state

Summary for 8CTD

• Entry DOI: 10.2210/pdb8ctd/pdb
• EMDB information: 26986
• Descriptor: Excitatory amino acid transporter 3, GLUTAMIC ACID, SODIUM ION, ... (4 entities in total)
• Functional Keywords: transport protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 57537.55

Authors

Qiu, B.,Boudker, O. (deposition date: 2022-05-14, release date: 2023-05-10, Last modification date: 2024-06-12)

Primary citation

Qiu, B.,Boudker, O.
Symport and antiport mechanisms of human glutamate transporters.
Nat Commun, 14:2579-2579, 2023

PubMed Abstract: Excitatory amino acid transporters (EAATs) uptake glutamate into glial cells and neurons. EAATs achieve million-fold transmitter gradients by symporting it with three sodium ions and a proton, and countertransporting a potassium ion via an elevator mechanism. Despite the availability of structures, the symport and antiport mechanisms still need to be clarified. We report high-resolution cryo-EM structures of human EAAT3 bound to the neurotransmitter glutamate with symported ions, potassium ions, sodium ions alone, or without ligands. We show that an evolutionarily conserved occluded translocation intermediate has a dramatically higher affinity for the neurotransmitter and the countertransported potassium ion than outward- or inward-facing transporters and plays a crucial role in ion coupling. We propose a comprehensive ion coupling mechanism involving a choreographed interplay between bound solutes, conformations of conserved amino acid motifs, and movements of the gating hairpin and the substrate-binding domain.

PubMed: 37142617
DOI: 10.1038/s41467-023-38120-5

Experimental method

ELECTRON MICROSCOPY (3.42 Å)