9MRM

Desensitized state 2 of the GluA2-gamma2 complex prepared at 37 degrees C

9MRM の概要

• エントリーDOI: 10.2210/pdb9mrm/pdb
• EMDBエントリー: 48559
• 分子名称: Isoform Flip of Glutamate receptor 2, TARPgamma2, GLUTAMIC ACID (3 entities in total)
• 機能のキーワード: ligand-gated ion channel, transport protein
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 260822.81

構造登録者

Kumar Mondal, A.,Twomey, E.C. (登録日: 2025-01-08, 公開日: 2025-03-26, 最終更新日: 2025-05-21)

主引用文献

Kumar Mondal, A.,Carrillo, E.,Jayaraman, V.,Twomey, E.C.
Glutamate gating of AMPA-subtype iGluRs at physiological temperatures.
Nature, 641:788-796, 2025

PubMed Abstract: Ionotropic glutamate receptors (iGluRs) are tetrameric ligand-gated ion channels that mediate most excitatory neurotransmission. iGluRs are gated by glutamate, where on glutamate binding, they open their ion channels to enable cation influx into postsynaptic neurons, initiating signal transduction. The structural mechanics of how glutamate gating occurs in full-length iGluRs is not well understood. Here, using the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid subtype iGluR (AMPAR), we identify the glutamate-gating mechanism. AMPAR activation by glutamate is augmented at physiological temperatures. By preparing AMPARs for cryogenic-electron microscopy at these temperatures, we captured the glutamate-gating mechanism. Activation by glutamate initiates ion channel opening that involves all ion channel helices hinging away from the pore axis in a motif that is conserved across all iGluRs. Desensitization occurs when the local dimer pairs decouple and enables closure of the ion channel below through restoring the channel hinges and refolding the channel gate. Our findings define how glutamate gates iGluRs, provide foundations for therapeutic design and demonstrate how physiological temperatures can alter iGluR function.

PubMed: 40140570
DOI: 10.1038/s41586-025-08770-0

実験手法

ELECTRON MICROSCOPY (4.52 Å)