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	Gating and modulation of a hetero-octameric AMPA glutamate receptor.
ジャーナル・号・ページ	Nature, Vol. 594, Issue 7863, Page 454-458, Year 2021
掲載日	2021年6月2日
著者	Danyang Zhang / Jake F Watson / Peter M Matthews / Ondrej Cais / Ingo H Greger /
PubMed 要旨	AMPA receptors (AMPARs) mediate the majority of excitatory transmission in the brain and enable the synaptic plasticity that underlies learning. A diverse array of AMPAR signalling complexes are ...AMPA receptors (AMPARs) mediate the majority of excitatory transmission in the brain and enable the synaptic plasticity that underlies learning. A diverse array of AMPAR signalling complexes are established by receptor auxiliary subunits, which associate with the AMPAR in various combinations to modulate trafficking, gating and synaptic strength. However, their mechanisms of action are poorly understood. Here we determine cryo-electron microscopy structures of the heteromeric GluA1-GluA2 receptor assembled with both TARP-γ8 and CNIH2, the predominant AMPAR complex in the forebrain, in both resting and active states. Two TARP-γ8 and two CNIH2 subunits insert at distinct sites beneath the ligand-binding domains of the receptor, with site-specific lipids shaping each interaction and affecting the gating regulation of the AMPARs. Activation of the receptor leads to asymmetry between GluA1 and GluA2 along the ion conduction path and an outward expansion of the channel triggers counter-rotations of both auxiliary subunit pairs, promoting the active-state conformation. In addition, both TARP-γ8 and CNIH2 pivot towards the pore exit upon activation, extending their reach for cytoplasmic receptor elements. CNIH2 achieves this through its uniquely extended M2 helix, which has transformed this endoplasmic reticulum-export factor into a powerful AMPAR modulator that is capable of providing hippocampal pyramidal neurons with their integrative synaptic properties.
リンク	Nature / PubMed:34079129 / PubMed Central
手法	EM (単粒子)
解像度	3.1 - 3.6 Å
構造データ	12802 7oca EMDB-12802, PDB-7oca: Resting state full-length GluA1/A2 heterotertramer in complex with TARP gamma 8 and CNIH2 手法: EM (単粒子) / 解像度: 3.4 Å 12803 7occ EMDB-12803, PDB-7occ: NTD of resting state GluA1/A2 heterotertramer 手法: EM (単粒子) / 解像度: 3.4 Å 12804 7ocd EMDB-12804, PDB-7ocd: Resting state GluA1/A2 heterotetramer in complex with auxiliary subunit TARP gamma 8 (LBD-TMD) 手法: EM (単粒子) / 解像度: 3.5 Å 12805 7oce EMDB-12805, PDB-7oce: Resting state GluA1/A2 AMPA receptor in complex with TARP gamma 8 and CNIH2 (LBD-TMD) 手法: EM (単粒子) / 解像度: 3.1 Å 12806 7ocf EMDB-12806, PDB-7ocf: Active state GluA1/A2 AMPA receptor in complex with TARP gamma 8 and CNIH2 (LBD-TMD) 手法: EM (単粒子) / 解像度: 3.6 Å
化合物	ChemComp-E2Q: 6-nitro-2,3-bis(oxidanylidene)-1,4-dihydrobenzo[f]quinoxaline-7-sulfonamide / アンタゴニストYM / NBQX 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 ChemComp-PC1: 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE / リン脂質YM / ホスファチジルコリン ChemComp-CLR: CHOLESTEROL / コレステロ-ル / コレステロール ChemComp-CYZ: CYCLOTHIAZIDE / (3S)-6-クロロ-3,4-ジヒドロ-3-[(1S,4S,5S)-ビシクロ[2.2.1]ヘプタ-2-エン-5-イル](以下略) / Cyclothiazide ChemComp-GLU: GLUTAMIC ACID / グルタミン酸 / グルタミン酸
由来	rattus norvegicus (ドブネズミ)
キーワード	MEMBRANE PROTEIN (膜タンパク質) / AMPAR / ion channels (イオンチャネル) / neurotransmission