EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Glutamate gating of AMPA-subtype iGluRs at physiological temperatures.
ジャーナル・号・ページ	Nature, Vol. 641, Issue 8063, Page 788-796, Year 2025
掲載日	2025年3月26日
著者	Anish Kumar Mondal / Elisa Carrillo / Vasanthi Jayaraman / Edward C Twomey /
PubMed 要旨	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 ...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.
リンク	Nature / PubMed:40140570 / PubMed Central
手法	EM (単粒子)
解像度	3.46 - 4.78 Å
構造データ	46872 9dhp EMDB-46872, PDB-9dhp: Resting state 1 of the GluA2-gamma2 complex 手法: EM (単粒子) / 解像度: 4.18 Å 46873 9dhq EMDB-46873, PDB-9dhq: Resting state 2 of the GluA2-gamma2 complex 手法: EM (単粒子) / 解像度: 4.78 Å 46874 9dhr EMDB-46874, PDB-9dhr: Glutamate activated state of the GluA2-gamma2 complex 手法: EM (単粒子) / 解像度: 3.54 Å 46875 9dhs EMDB-46875, PDB-9dhs: Desensitized state 1 of the GluA2-gamma2 complex 手法: EM (単粒子) / 解像度: 4.48 Å 46876 9dht EMDB-46876, PDB-9dht: Desensitized state 2 of the GluA2-gamma2 complex 手法: EM (単粒子) / 解像度: 4.31 Å 48557 9mrk EMDB-48557, PDB-9mrk: Glutamate activated state of the GluA2-gamma2 complex prepared at 37 degrees C 手法: EM (単粒子) / 解像度: 3.62 Å 48558 9mrl EMDB-48558, PDB-9mrl: Desensitized state 1 of the GluA2-gamma2 complex prepared at 37 degrees C 手法: EM (単粒子) / 解像度: 4.17 Å 48559 9mrm EMDB-48559, PDB-9mrm: Desensitized state 2 of the GluA2-gamma2 complex prepared at 37 degrees C 手法: EM (単粒子) / 解像度: 4.52 Å 48560 9mrn EMDB-48560, PDB-9mrn: Consensus glutamate activated state of the GluA2-gamma2 complex 手法: EM (単粒子) / 解像度: 3.46 Å
化合物	ChemComp-GLU: GLUTAMIC ACID / グルタミン酸
由来	rattus norvegicus (ドブネズミ) mus musculus (ハツカネズミ)
キーワード	TRANSPORT PROTEIN / ligand-gated ion channel / ionotropic glutamate receptor / ampa receptor / ion channel / ligand gated ion channel