6IRH

Structure of the human GluN1/GluN2A NMDA receptor in the glutamate/glycine-bound state at pH 6.3, Class III

6IRH の概要

• エントリーDOI: 10.2210/pdb6irh/pdb
• 関連するPDBエントリー: 6IRA 6IRF 6IRG
• EMDBエントリー: 9714 9715 9716 9717
• 分子名称: Glutamate receptor ionotropic, NMDA 1, Glutamate receptor ionotropic, NMDA 2A (2 entities in total)
• 機能のキーワード: ionotropic glutamate receptors, nmda receptors, synaptic protein, 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: 379056.78

構造登録者

Zhang, J.,Chang, S.,Zhang, X.,Zhu, S. (登録日: 2018-11-12, 公開日: 2019-01-16, 最終更新日: 2019-06-05)

主引用文献

Zhang, J.B.,Chang, S.,Xu, P.,Miao, M.,Wu, H.,Zhang, Y.,Zhang, T.,Wang, H.,Zhang, J.,Xie, C.,Song, N.,Luo, C.,Zhang, X.,Zhu, S.
Structural Basis of the Proton Sensitivity of Human GluN1-GluN2A NMDA Receptors
Cell Rep, 25:3582-3590.e4, 2018

PubMed Abstract: N-methyl-D-aspartate (NMDA) receptors are critical for synaptic development and plasticity. While glutamate is the primary agonist, protons can modulate NMDA receptor activity at synapses during vesicle exocytosis by mechanisms that are unknown. We used cryo-electron microscopy to solve the structures of the human GluN1-GluN2A NMDA receptor at pH 7.8 and pH 6.3. Our structures demonstrate that the proton sensor predominantly resides in the N-terminal domain (NTD) of the GluN2A subunit and reveal the allosteric coupling mechanism between the proton sensor and the channel gate. Under high-pH conditions, the GluN2A-NTD adopts an "open-and-twisted" conformation. However, upon protonation at the lower pH, the GluN2A-NTD transits from an open- to closed-cleft conformation, causing rearrangements between the tetrameric NTDs and agonist-binding domains. The conformational mobility observed in our structures (presumably from protonation) is supported by molecular dynamics simulation. Our findings reveal the structural mechanisms by which protons allosterically inhibit human GluN1-GluN2A receptor activity.

PubMed: 30590034
DOI: 10.1016/j.celrep.2018.11.071

実験手法

ELECTRON MICROSCOPY (7.8 Å)