5B3J

Activation of NMDA receptors and the mechanism of inhibition by ifenprodil

5B3J の概要

• エントリーDOI: 10.2210/pdb5b3j/pdb
• 分子名称: NMDA glutamate receptor subunit, Glutamate receptor ionotropic, NMDA 2B, Fab, heavy chain, ... (6 entities in total)
• 機能のキーワード: nmda receptor, transport protein
• 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: Q00960
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 263802.81

構造登録者

Tajima, N.,Karakas, E.,Grant, T.,Simorowski, N.,Diaz-Avalos, R.,Grigorieff, N.,Furukawa, H. (登録日: 2016-03-01, 公開日: 2016-05-11, 最終更新日: 2024-10-23)

主引用文献

Tajima, N.,Karakas, E.,Grant, T.,Simorowski, N.,Diaz-Avalos, R.,Grigorieff, N.,Furukawa, H.
Activation of NMDA receptors and the mechanism of inhibition by ifenprodil
Nature, 534:63-68, 2016

PubMed Abstract: The physiology of N-methyl-d-aspartate (NMDA) receptors is fundamental to brain development and function. NMDA receptors are ionotropic glutamate receptors that function as heterotetramers composed mainly of GluN1 and GluN2 subunits. Activation of NMDA receptors requires binding of neurotransmitter agonists to a ligand-binding domain (LBD) and structural rearrangement of an amino-terminal domain (ATD). Recent crystal structures of GluN1-GluN2B NMDA receptors bound to agonists and an allosteric inhibitor, ifenprodil, represent the allosterically inhibited state. However, how the ATD and LBD move to activate the NMDA receptor ion channel remains unclear. Here we applied X-ray crystallography, single-particle electron cryomicroscopy and electrophysiology to rat NMDA receptors to show that, in the absence of ifenprodil, the bi-lobed structure of GluN2 ATD adopts an open conformation accompanied by rearrangement of the GluN1-GluN2 ATD heterodimeric interface, altering subunit orientation in the ATD and LBD and forming an active receptor conformation that gates the ion channel.

PubMed: 27135925
DOI: 10.1038/nature17679

実験手法

X-RAY DIFFRACTION (2.9 Å)