5IPV

Cryo-EM structure of GluN1/GluN2B NMDA receptor in the DCKA/D-APV-bound conformation, state 1

5IPV の概要

• エントリーDOI: 10.2210/pdb5ipv/pdb
• 関連するPDBエントリー: 5IOU 5IOV 5IPQ 5IPR 5IPS 5IPT 5IPU
• EMDBエントリー: 8097 8098 8101 8102 8103 8104 8105 8106
• 分子名称: N-methyl-D-aspartate receptor subunit NR1-8a, Ionotropic glutamate receptor subunit NR2B (2 entities in total)
• 機能のキーワード: ligand-gated ion channel, synaptic transmission, signaling protein
• 由来する生物種: Xenopus laevis (African clawed frog); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 371771.95

構造登録者

Zhu, S.,Stein, A.R.,Yoshioka, C.,Lee, C.H.,Goehring, A.,McHaourab, S.H.,Gouaux, E. (登録日: 2016-03-10, 公開日: 2016-04-20, 最終更新日: 2024-03-06)

主引用文献

Zhu, S.,Stein, R.A.,Yoshioka, C.,Lee, C.H.,Goehring, A.,Mchaourab, H.S.,Gouaux, E.
Mechanism of NMDA Receptor Inhibition and Activation.
Cell, 165:704-714, 2016

PubMed Abstract: N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated, calcium-permeable ion channels that mediate synaptic transmission and underpin learning and memory. NMDAR dysfunction is directly implicated in diseases ranging from seizure to ischemia. Despite its fundamental importance, little is known about how the NMDAR transitions between inactive and active states and how small molecules inhibit or activate ion channel gating. Here, we report electron cryo-microscopy structures of the GluN1-GluN2B NMDA receptor in an ensemble of competitive antagonist-bound states, an agonist-bound form, and a state bound with agonists and the allosteric inhibitor Ro25-6981. Together with double electron-electron resonance experiments, we show how competitive antagonists rupture the ligand binding domain (LBD) gating "ring," how agonists retain the ring in a dimer-of-dimers configuration, and how allosteric inhibitors, acting within the amino terminal domain, further stabilize the LBD layer. These studies illuminate how the LBD gating ring is fundamental to signal transduction and gating in NMDARs.

PubMed: 27062927
DOI: 10.1016/j.cell.2016.03.028

実験手法

ELECTRON MICROSCOPY (9.25 Å)