8CUA

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

8CUA の概要

• エントリーDOI: 10.2210/pdb8cua/pdb
• EMDBエントリー: 26997
• 分子名称: Excitatory amino acid transporter 3, POTASSIUM ION, MERCURY (II) ION, ... (4 entities in total)
• 機能のキーワード: transport protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 172081.65

構造登録者

Qiu, B.,Boudker, O. (登録日: 2022-05-17, 公開日: 2023-05-10, 最終更新日: 2024-10-09)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (2.44 Å)