7AWM

Structure of the thermostabilized EAAT1 cryst mutant in complex with L-ASP, three sodium ions and the allosteric inhibitor UCPH101

7AWM の概要

• エントリーDOI: 10.2210/pdb7awm/pdb
• 分子名称: Excitatory amino acid transporter 1,Neutral amino acid transporter B(0),Excitatory amino acid transporter 1, SODIUM ION, ASPARTIC ACID, ... (5 entities in total)
• 機能のキーワード: excitatory amino acid transporter 1, human glutamate transporter, slc1a3, allosteric inhibitor ucph101, membrane protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 57274.25

構造登録者

Canul-Tec, J.C.,Legrand, P.,Reyes, N. (登録日: 2020-11-08, 公開日: 2021-10-13, 最終更新日: 2024-01-31)

主引用文献

Canul-Tec, J.C.,Kumar, A.,Dhenin, J.,Assal, R.,Legrand, P.,Rey, M.,Chamot-Rooke, J.,Reyes, N.
The ion-coupling mechanism of human excitatory amino acid transporters.
Embo J., 41:e108341-e108341, 2022

PubMed Abstract: Excitatory amino acid transporters (EAATs) maintain glutamate gradients in the brain essential for neurotransmission and to prevent neuronal death. They use ionic gradients as energy source and co-transport transmitter into the cytoplasm with Na and H , while counter-transporting K to re-initiate the transport cycle. However, the molecular mechanisms underlying ion-coupled transport remain incompletely understood. Here, we present 3D X-ray crystallographic and cryo-EM structures, as well as thermodynamic analysis of human EAAT1 in different ion bound conformations, including elusive counter-transport ion bound states. Binding energies of Na and H , and unexpectedly Ca , are coupled to neurotransmitter binding. Ca competes for a conserved Na site, suggesting a regulatory role for Ca in glutamate transport at the synapse, while H binds to a conserved glutamate residue stabilizing substrate occlusion. The counter-transported ion binding site overlaps with that of glutamate, revealing the K -based mechanism to exclude the transmitter during the transport cycle and to prevent its neurotoxic release on the extracellular side.

PubMed: 34747040
DOI: 10.15252/embj.2021108341

実験手法

X-RAY DIFFRACTION (3.25 Å)