6DM0

Open state GluA2 in complex with STZ and blocked by IEM-1460, after micelle signal subtraction

6DM0 の概要

• エントリーDOI: 10.2210/pdb6dm0/pdb
• EMDBエントリー: 7960
• 分子名称: Glutamate receptor 2,Voltage-dependent calcium channel gamma-2 subunit, GLUTAMIC ACID, CYCLOTHIAZIDE, ... (4 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: 463155.66

構造登録者

Twomey, E.C.,Yelshanskaya, M.V.,Vassilevski, A.A.,Sobolevsky, A.I. (登録日: 2018-06-04, 公開日: 2018-08-22, 最終更新日: 2024-11-13)

主引用文献

Twomey, E.C.,Yelshanskaya, M.V.,Vassilevski, A.A.,Sobolevsky, A.I.
Mechanisms of Channel Block in Calcium-Permeable AMPA Receptors.
Neuron, 99:956-968.e4, 2018

PubMed Abstract: AMPA receptors mediate fast excitatory neurotransmission and are critical for CNS development and function. Calcium-permeable subsets of AMPA receptors are strongly implicated in acute and chronic neurological disorders. However, despite the clinical importance, the therapeutic landscape for specifically targeting them, and not the calcium-impermeable AMPA receptors, remains largely undeveloped. To address this problem, we used cryo-electron microscopy and electrophysiology to investigate the mechanisms by which small-molecule blockers selectively inhibit ion channel conductance in calcium-permeable AMPA receptors. We determined the structures of calcium-permeable GluA2 AMPA receptor complexes with the auxiliary subunit stargazin bound to channel blockers, including the orb weaver spider toxin AgTx-636, the spider toxin analog NASPM, and the adamantane derivative IEM-1460. Our structures provide insights into the architecture of the blocker binding site and the mechanism of trapping, which are critical for development of small molecules that specifically target calcium-permeable AMPA receptors.

PubMed: 30122377
DOI: 10.1016/j.neuron.2018.07.027

実験手法

ELECTRON MICROSCOPY (4.4 Å)