6WHW

GluN1b-GluN2B NMDA receptor in complex with GluN2B antagonist SDZ 220-040, class 1

6WHW の概要

• エントリーDOI: 10.2210/pdb6whw/pdb
• EMDBエントリー: 21678
• 分子名称: Ionotropic glutamate receptor , NMDA receptor GluN1b, Ionotropic glutamate receptor , NMDA receptor GluN2B, (2S)-2-amino-3-[2',4'-dichloro-4-hydroxy-5-(phosphonomethyl)biphenyl-3-yl]propanoic acid, ... (4 entities in total)
• 機能のキーワード: nmdars, ligand-gated ion channels, metal transport, ionotropic glutamate receptor, membrane protein, glun2b antagonist
• 由来する生物種: Rattus norvegicus (Rat); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 415145.76

構造登録者

Chou, T.,Tajima, N.,Furukawa, H. (登録日: 2020-04-08, 公開日: 2020-07-15, 最終更新日: 2020-08-05)

主引用文献

Chou, T.H.,Tajima, N.,Romero-Hernandez, A.,Furukawa, H.
Structural Basis of Functional Transitions in Mammalian NMDA Receptors.
Cell, 182:357-371.e13, 2020

PubMed Abstract: Excitatory neurotransmission meditated by glutamate receptors including N-methyl-D-aspartate receptors (NMDARs) is pivotal to brain development and function. NMDARs are heterotetramers composed of GluN1 and GluN2 subunits, which bind glycine and glutamate, respectively, to activate their ion channels. Despite importance in brain physiology, the precise mechanisms by which activation and inhibition occur via subunit-specific binding of agonists and antagonists remain largely unknown. Here, we show the detailed patterns of conformational changes and inter-subunit and -domain reorientation leading to agonist-gating and subunit-dependent competitive inhibition by providing multiple structures in distinct ligand states at 4 Å or better. The structures reveal that activation and competitive inhibition by both GluN1 and GluN2 antagonists occur by controlling the tension of the linker between the ligand-binding domain and the transmembrane ion channel of the GluN2 subunit. Our results provide detailed mechanistic insights into NMDAR pharmacology, activation, and inhibition, which are fundamental to the brain physiology.

PubMed: 32610085
DOI: 10.1016/j.cell.2020.05.052

実験手法

ELECTRON MICROSCOPY (4.09 Å)