9IYQ

Structure of the human GluN1-N2B NMDA receptors in the Mg2+ free state

9IYQ の概要

• エントリーDOI: 10.2210/pdb9iyq/pdb
• EMDBエントリー: 61001
• 分子名称: Glutamate receptor ionotropic, NMDA 1, Glutamate receptor ionotropic, NMDA 2B, GLYCINE, ... (5 entities in total)
• 機能のキーワード: glun1-n2b nmda receptors, 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: 381626.38

構造登録者

Huang, X.,Sun, X.,Zhu, S. (登録日: 2024-07-31, 公開日: 2025-03-05, 最終更新日: 2025-07-23)

主引用文献

Huang, X.,Sun, X.,Wang, Q.,Zhang, J.,Wen, H.,Chen, W.J.,Zhu, S.
Structural insights into the diverse actions of magnesium on NMDA receptors.
Neuron, 113:1006-, 2025

PubMed Abstract: Magnesium (Mg) is a key regulatory ion of N-methyl-ᴅ-aspartate (NMDA) receptors, including conferring them to function as coincidence detectors for excitatory synaptic transmission. However, the structural basis underlying the Mg action on NMDA receptors remains unclear. Here, we report the cryo-EM structures of GluN1-N2B receptors and identify three distinct Mg-binding pockets. Specifically, site Ⅰ is located at the selectivity filter where an asparagine ring forms coordination bonds with Mg and is responsible for the voltage-dependent block. Sites Ⅱ and Ⅲ are located at the N-terminal domain (NTD) of the GluN2B subunit and involved in the allosteric potentiation and inhibition, respectively. Site Ⅱ consists of three acidic residues, and the combination of three mutations abolishes the GluN2B-specific Mg potentiation, while site Ⅲ overlaps with the Zn pocket, and mutations here significantly reduce the inhibition. Our study enhances the understanding of multifaceted roles of Mg in NMDA receptors and synaptic plasticity.

PubMed: 40010346
DOI: 10.1016/j.neuron.2025.01.021

実験手法

ELECTRON MICROSCOPY (3.18 Å)