9UNK

native NMDA receptor-GluN1/N2B in the closed state

9UNK の概要

• エントリーDOI: 10.2210/pdb9unk/pdb
• EMDBエントリー: 64354
• 分子名称: Glutamate receptor ionotropic, NMDA 1, Glutamate receptor ionotropic, NMDA 2B, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: native, nmda receptor, ionotropic ion channel, excitatory neurotransmitter, membrane protein
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 374093.32

構造登録者

Yu, J.,Xu, R.S.,Ge, J.P. (登録日: 2025-04-23, 公開日: 2026-02-18, 最終更新日: 2026-02-25)

主引用文献

Xu, R.,Jiang, Q.,Xu, H.,Zhang, L.,Hu, X.,Lu, Z.,Deng, H.,Xiong, H.,Zhang, S.,Chen, Z.,Ge, Y.,Zhu, Z.,Zhang, Y.,Chen, Y.,Ge, J.,Yu, J.
Conformational diversity and fully opening mechanism of native NMDA receptor.
Nature, 2026

PubMed Abstract: N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels that mediate excitatory neurotransmission throughout the brain. As obligate heterotetramers, their activation requires the binding of both glycine and glutamate. Although recent structural studies have provided insights into endogenous receptors from select brain regions, most previous work has relied on recombinant receptors and engineered constructs, which limits our understanding of native NMDARs across the whole brain. Here we identify and resolve ten distinct native NMDAR assemblies from the whole-brain tissue of female C57BL/6 mice using immunoaffinity purification, single-molecule total internal reflection fluorescence microscopy and cryo-electron microscopy. Analyses of the GluN1-GluN2A(S1), GluN1-GluN2A(S2), GluN1-GluN2A(S3), GluN1-GluN2B, GluN1-GluN2A-GluN2B(S1), GluN1-GluN2A-GluN2B(S2), GluN1-GluN2A-GluNX(S1), GluN1-GluN2A-GluNX(S2), GluN1-GluN2B-GluNX and GluN1-GluNX structures reveal that GluN2A is the most prevalent subunit across assemblies. Moreover, the substantial conformational flexibility observed in the GluN2A amino-terminal domain may explain its fast kinetics and dominant role in gating. Dynamic movements of S-ketamine were also captured at the channel vestibule, as was pore dilation in both the GluN1 and GluN2B subunits of a native GluN1-GluN2B receptor. The latter observation represents a previously unknown fully open state of NMDAR. Our large collection of heterogeneous NMDAR structures from whole brain reveals previously unrecognized properties of conformational diversity and channel dilation.

PubMed: 41673155
DOI: 10.1038/s41586-026-10139-w

実験手法

ELECTRON MICROSCOPY (3.37 Å)