7EOU

Structure of the human GluN1/GluN2A NMDA receptor in the glycine/glutamate/GNE-6901/9-AA bound state

7EOU の概要

• エントリーDOI: 10.2210/pdb7eou/pdb
• EMDBエントリー: 31231
• 分子名称: Glutamate receptor ionotropic, NMDA 2A, Glutamate receptor ionotropic, NMDA 1, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: nmda receptor, membrane protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 385950.98

構造登録者

Wang, H.,Zhu, S. (登録日: 2021-04-22, 公開日: 2021-06-30, 最終更新日: 2024-10-16)

主引用文献

Wang, H.,Lv, S.,Stroebel, D.,Zhang, J.,Pan, Y.,Huang, X.,Zhang, X.,Paoletti, P.,Zhu, S.
Gating mechanism and a modulatory niche of human GluN1-GluN2A NMDA receptors.
Neuron, 109:2443-2456.e5, 2021

PubMed Abstract: N-methyl-D-aspartate (NMDA) receptors are glutamate-gated calcium-permeable ion channels that are widely implicated in synaptic transmission and plasticity. Here, we report a gallery of cryo-electron microscopy (cryo-EM) structures of the human GluN1-GluN2A NMDA receptor at an overall resolution of 4 Å in complex with distinct ligands or modulators. In the full-length context of GluN1-GluN2A receptors, we visualize the competitive antagonists bound to the ligand-binding domains (LBDs) of GluN1 and GluN2A subunits, respectively. We reveal that the binding of positive allosteric modulator shortens the distance between LBDs and the transmembrane domain (TMD), which further stretches the opening of the gate. In addition, we unexpectedly visualize the binding cavity of the "foot-in-the-door" blocker 9-aminoacridine within the LBD-TMD linker region, differing from the conventional "trapping" blocker binding site at the vestibule within the TMD. Our study provides molecular insights into the crosstalk between LBDs and TMD during channel activation, inhibition, and allosteric transition.

PubMed: 34186027
DOI: 10.1016/j.neuron.2021.05.031

実験手法

ELECTRON MICROSCOPY (4.3 Å)