5WEK

GluA2 bound to antagonist ZK and GSG1L in digitonin, state 1

5WEK の概要

• エントリーDOI: 10.2210/pdb5wek/pdb
• EMDBエントリー: 8819 8820 8821 8822 8823
• 分子名称: Chimera of Glutamate receptor 2,Germ cell-specific gene 1-like protein, {[7-morpholin-4-yl-2,3-dioxo-6-(trifluoromethyl)-3,4-dihydroquinoxalin-1(2H)-yl]methyl}phosphonic acid (2 entities in total)
• 機能のキーワード: ion channel, transport protein
• 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: 471521.86

構造登録者

Twomey, E.C.,Yelshanskaya, M.V.,Grassucci, R.A.,Frank, J.,Sobolevsky, A.I. (登録日: 2017-07-10, 公開日: 2017-08-02, 最終更新日: 2024-11-13)

主引用文献

Twomey, E.C.,Yelshanskaya, M.V.,Grassucci, R.A.,Frank, J.,Sobolevsky, A.I.
Channel opening and gating mechanism in AMPA-subtype glutamate receptors.
Nature, 549:60-65, 2017

PubMed Abstract: AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-subtype ionotropic glutamate receptors mediate fast excitatory neurotransmission throughout the central nervous system. Gated by the neurotransmitter glutamate, AMPA receptors are critical for synaptic strength, and dysregulation of AMPA receptor-mediated signalling is linked to numerous neurological diseases. Here we use cryo-electron microscopy to solve the structures of AMPA receptor-auxiliary subunit complexes in the apo, antagonist- and agonist-bound states and determine the iris-like mechanism of ion channel opening. The ion channel selectivity filter is formed by the extended portions of the re-entrant M2 loops, while the helical portions of M2 contribute to extensive hydrophobic interfaces between AMPA receptor subunits in the ion channel. We show how the permeation pathway changes upon channel opening and identify conformational changes throughout the entire AMPA receptor that accompany activation and desensitization. Our findings provide a framework for understanding gating across the family of ionotropic glutamate receptors and the role of AMPA receptors in excitatory neurotransmission.

PubMed: 28737760
DOI: 10.1038/nature23479

実験手法

ELECTRON MICROSCOPY (4.6 Å)