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	Structural Basis of Functional Transitions in Mammalian NMDA Receptors.
ジャーナル・号・ページ	Cell, Vol. 182, Issue 2, Page 357-371.e13, Year 2020
掲載日	2020年7月23日
著者	Tsung-Han Chou / Nami Tajima / Annabel Romero-Hernandez / Hiro Furukawa /
PubMed 要旨	Excitatory neurotransmission meditated by glutamate receptors including N-methyl-D-aspartate receptors (NMDARs) is pivotal to brain development and function. NMDARs are heterotetramers composed of ...Excitatory neurotransmission meditated by glutamate receptors including N-methyl-D-aspartate receptors (NMDARs) is pivotal to brain development and function. NMDARs are heterotetramers composed of GluN1 and GluN2 subunits, which bind glycine and glutamate, respectively, to activate their ion channels. Despite importance in brain physiology, the precise mechanisms by which activation and inhibition occur via subunit-specific binding of agonists and antagonists remain largely unknown. Here, we show the detailed patterns of conformational changes and inter-subunit and -domain reorientation leading to agonist-gating and subunit-dependent competitive inhibition by providing multiple structures in distinct ligand states at 4 Å or better. The structures reveal that activation and competitive inhibition by both GluN1 and GluN2 antagonists occur by controlling the tension of the linker between the ligand-binding domain and the transmembrane ion channel of the GluN2 subunit. Our results provide detailed mechanistic insights into NMDAR pharmacology, activation, and inhibition, which are fundamental to the brain physiology.
リンク	Cell / PubMed:32610085 / PubMed Central
手法	EM (単粒子) / X線回折
解像度	2.092 - 4.39 Å
構造データ	21673 6whr EMDB-21673, PDB-6whr: GluN1b-GluN2B NMDA receptor in non-active 2 conformation at 4 angstrom resolution 手法: EM (単粒子) / 解像度: 3.99 Å 21674 6whs EMDB-21674, PDB-6whs: GluN1b-GluN2B NMDA receptor in non-active 1 conformation at 3.95 angstrom resolution 手法: EM (単粒子) / 解像度: 4.0 Å 21675 6wht EMDB-21675, PDB-6wht: GluN1b-GluN2B NMDA receptor in active conformation at 4.4 angstrom resolution 手法: EM (単粒子) / 解像度: 4.39 Å 21676 6whu EMDB-21676, PDB-6whu: GluN1b-GluN2B NMDA receptor in complex with SDZ 220-040 and L689,560, class 1 手法: EM (単粒子) / 解像度: 3.93 Å 21677 6whv EMDB-21677, PDB-6whv: GluN1b-GluN2B NMDA receptor in complex with SDZ 220-040 and L689,560, class 2 手法: EM (単粒子) / 解像度: 4.05 Å 21678 6whw EMDB-21678, PDB-6whw: GluN1b-GluN2B NMDA receptor in complex with GluN2B antagonist SDZ 220-040, class 1 手法: EM (単粒子) / 解像度: 4.09 Å 21679 6whx EMDB-21679, PDB-6whx: GluN1b-GluN2B NMDA receptor in complex with GluN2B antagonist SDZ 220-040, class 2 手法: EM (単粒子) / 解像度: 4.09 Å 21680 6why EMDB-21680, PDB-6why: GluN1b-GluN2B NMDA receptor in complex with GluN1 antagonist L689,560, class 1 手法: EM (単粒子) / 解像度: 4.03 Å 21681 6wi0 EMDB-21681, PDB-6wi0: GluN1b-GluN2B NMDA receptor in complex with GluN1 antagonist L689,560, class 2 手法: EM (単粒子) / 解像度: 4.27 Å 21682 6wi1 EMDB-21682, PDB-6wi1: GluN1b-GluN2B NMDA receptor in active conformation stabilized by inter-GluN1b-GluN2B subunit cross-linking 手法: EM (単粒子) / 解像度: 3.62 Å PDB-6usu: Crystal structure of GluN1/GluN2A ligand-binding domain in complex with L689,560 and glutamate 手法: X-RAY DIFFRACTION / 解像度: 2.092 Å PDB-6usv: Crystal structure of GluN1/GluN2A ligand-binding domain in complex with glycine and SDZ 220-040 手法: X-RAY DIFFRACTION / 解像度: 2.304 Å
化合物	ChemComp-QGM: (2R,4S)-5,7-dichloro-4-[(phenylcarbamoyl)amino]-1,2,3,4-tetrahydroquinoline-2-carboxylic acid / (-)-L-689560 ChemComp-GLU: GLUTAMIC ACID / グルタミン酸 / グルタミン酸 ChemComp-HOH: WATER / 水 ChemComp-GLY: GLYCINE / グリシン / グリシン ChemComp-QGP: (2S)-2-amino-3-[2',4'-dichloro-4-hydroxy-5-(phosphonomethyl)biphenyl-3-yl]propanoic acid / SDZ-220-040 ChemComp-GOL: GLYCEROL / グリセロ-ル / グリセリン ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン / N-アセチルグルコサミン
由来	rattus norvegicus (ドブネズミ)
キーワード	METAL TRANSPORT / NMDARs / LBD / Ion channels (イオンチャネル) / MEMBRANE PROTEIN (膜タンパク質) / Ligand-gated ion channels (リガンド依存性イオンチャネル) / Ionotropic glutamate receptor / GluN1 antagonist / GluN2B antagonist