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	Molecular mechanism of ligand gating and opening of NMDA receptor.
ジャーナル・号・ページ	Nature, Vol. 632, Issue 8023, Page 209-217, Year 2024
掲載日	2024年7月31日
著者	Tsung-Han Chou / Max Epstein / Russell G Fritzemeier / Nicholas S Akins / Srinu Paladugu / Elijah Z Ullman / Dennis C Liotta / Stephen F Traynelis / Hiro Furukawa /
PubMed 要旨	Glutamate transmission and activation of ionotropic glutamate receptors are the fundamental means by which neurons control their excitability and neuroplasticity. The N-methyl-D-aspartate receptor ...Glutamate transmission and activation of ionotropic glutamate receptors are the fundamental means by which neurons control their excitability and neuroplasticity. The N-methyl-D-aspartate receptor (NMDAR) is unique among all ligand-gated channels, requiring two ligands-glutamate and glycine-for activation. These receptors function as heterotetrameric ion channels, with the channel opening dependent on the simultaneous binding of glycine and glutamate to the extracellular ligand-binding domains (LBDs) of the GluN1 and GluN2 subunits, respectively. The exact molecular mechanism for channel gating by the two ligands has been unclear, particularly without structures representing the open channel and apo states. Here we show that the channel gate opening requires tension in the linker connecting the LBD and transmembrane domain (TMD) and rotation of the extracellular domain relative to the TMD. Using electron cryomicroscopy, we captured the structure of the GluN1-GluN2B (GluN1-2B) NMDAR in its open state bound to a positive allosteric modulator. This process rotates and bends the pore-forming helices in GluN1 and GluN2B, altering the symmetry of the TMD channel from pseudofourfold to twofold. Structures of GluN1-2B NMDAR in apo and single-liganded states showed that binding of either glycine or glutamate alone leads to distinct GluN1-2B dimer arrangements but insufficient tension in the LBD-TMD linker for channel opening. This mechanistic framework identifies a key determinant for channel gating and a potential pharmacological strategy for modulating NMDAR activity.
リンク	Nature / PubMed:39085540
手法	EM (単粒子)
解像度	3.13 - 4.05 Å
構造データ	43779 9are EMDB-43779, PDB-9are: Rat GluN1-GluN2B NMDA receptor channel in complex with glycine, glutamate, and EU-1622-A, in open-channel conformation 手法: EM (単粒子) / 解像度: 3.72 Å 43780 9arf EMDB-43780, PDB-9arf: Rat GluN1-GluN2B NMDA receptor channel in complex with glycine, glutamate, and EU-1622-A, in nonactive1 conformation 手法: EM (単粒子) / 解像度: 3.13 Å 43781 9arg EMDB-43781, PDB-9arg: Rat GluN1-GluN2B NMDA receptor channel in apo conformation 手法: EM (単粒子) / 解像度: 4.05 Å 43782 9arh EMDB-43782, PDB-9arh: Rat GluN1-GluN2B NMDA receptor channel in complex with glycine 手法: EM (単粒子) / 解像度: 3.69 Å 43783 9ari EMDB-43783, PDB-9ari: Rat GluN1-GluN2B NMDA receptor channel in complex with glutamate 手法: EM (単粒子) / 解像度: 3.9 Å 44586 9bib EMDB-44586, PDB-9bib: Rat GluN1-GluN2B NMDA receptor channel in complex with glycine, glutamate, and EU-1622-A, in open-channel conformation, C1 symmetry 手法: EM (単粒子) / 解像度: 3.81 Å
化合物	ChemComp-GLY: GLYCINE / グリシン ChemComp-GLU: GLUTAMIC ACID / グルタミン酸 ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン
由来	rattus norvegicus (ドブネズミ)
キーワード	MEMBRANE PROTEIN / Ligand-gated ion channel / ionotropic glutamate receptor / synaptic membrane protein / Ion channel