5UN1

Crystal structure of GluN1/GluN2B delta-ATD NMDA receptor

5UN1 の概要

• エントリーDOI: 10.2210/pdb5un1/pdb
• 分子名称: N-methyl-D-aspartate receptor subunit NR1-3a, Ionotropic glutamate receptor subunit NR2B, GLYCINE, ... (9 entities in total)
• 機能のキーワード: complex, arrangement, channel blocker, membrane proteins-inhibitor complex, membrane proteins/inhibitor
• 由来する生物種: Xenopus laevis (African clawed frog); 詳細
• 細胞内の位置: Cell membrane ; Multi- pass membrane protein : A7XY94
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 408395.75

構造登録者

Song, X.,Gouaux, E. (登録日: 2017-01-30, 公開日: 2018-02-07, 最終更新日: 2024-10-30)

主引用文献

Song, X.,Jensen, M.O.,Jogini, V.,Stein, R.A.,Lee, C.H.,Mchaourab, H.S.,Shaw, D.E.,Gouaux, E.
Mechanism of NMDA receptor channel block by MK-801 and memantine.
Nature, 556:515-519, 2018

PubMed Abstract: The NMDA (N-methyl-D-aspartate) receptor transduces the binding of glutamate and glycine, coupling it to the opening of a calcium-permeable ion channel . Owing to the lack of high-resolution structural studies of the NMDA receptor, the mechanism by which ion-channel blockers occlude ion permeation is not well understood. Here we show that removal of the amino-terminal domains from the GluN1-GluN2B NMDA receptor yields a functional receptor and crystals with good diffraction properties, allowing us to map the binding site of the NMDA receptor blocker, MK-801. This crystal structure, together with long-timescale molecular dynamics simulations, shows how MK-801 and memantine (a drug approved for the treatment of Alzheimer's disease) bind within the vestibule of the ion channel, promote closure of the ion channel gate and lodge between the M3-helix-bundle crossing and the M2-pore loops, physically blocking ion permeation.

PubMed: 29670280
DOI: 10.1038/s41586-018-0039-9

実験手法

X-RAY DIFFRACTION (3.6 Å)