登録情報 データベース : EMDB / ID : EMD-23284 構造の表示 ダウンロードとリンクタイトル native AMPA receptor マップデータ 詳細 試料複合体 : GluA1/A2-asymmetric-conformation bound to antibody fragments複合体 : GluA1/A2-asymmetric-conformation複合体 : 11B8 scFv複合体 : 15F1 Fabリガンド : x 10種 詳細 キーワード neurotransmitter / hippocampus / ion-channel / glycosylation / MEMBRANE PROTEIN機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
Phase 0 - rapid depolarisation / Phase 2 - plateau phase / Activation of AMPA receptors / Synaptic adhesion-like molecules / Cargo concentration in the ER / COPII-mediated vesicle transport / Unblocking of NMDA receptors, glutamate binding and activation / Trafficking of GluR2-containing AMPA receptors / LGI-ADAM interactions / axonal spine ... Phase 0 - rapid depolarisation / Phase 2 - plateau phase / Activation of AMPA receptors / Synaptic adhesion-like molecules / Cargo concentration in the ER / COPII-mediated vesicle transport / Unblocking of NMDA receptors, glutamate binding and activation / Trafficking of GluR2-containing AMPA receptors / LGI-ADAM interactions / axonal spine / Trafficking of AMPA receptors / positive regulation of locomotion involved in locomotory behavior / positive regulation of membrane potential / localization within membrane / cellular response to ammonium ion / response to sucrose / L-type voltage-gated calcium channel complex / neuron spine / myosin V binding / regulation of AMPA receptor activity / channel regulator activity / proximal dendrite / regulation of monoatomic ion transmembrane transport / response to arsenic-containing substance / cellular response to dsRNA / cellular response to L-glutamate / dendritic spine membrane / long-term synaptic depression / beta-2 adrenergic receptor binding / cellular response to peptide hormone stimulus / response to morphine / neuronal cell body membrane / protein kinase A binding / peptide hormone receptor binding / cellular response to amine stimulus / response to psychosocial stress / spinal cord development / perisynaptic space / AMPA glutamate receptor activity / response to lithium ion / behavioral response to pain / AMPA glutamate receptor complex / adenylate cyclase binding / ionotropic glutamate receptor complex / immunoglobulin binding / conditioned place preference / excitatory synapse / response to electrical stimulus / regulation of receptor recycling / G-protein alpha-subunit binding / positive regulation of excitatory postsynaptic potential / glutamate receptor binding / long-term memory / postsynaptic density, intracellular component / regulation of postsynaptic membrane neurotransmitter receptor levels / neuronal action potential / response to fungicide / glutamate-gated receptor activity / synapse assembly / vesicle-mediated transport / cellular response to brain-derived neurotrophic factor stimulus / glutamate-gated calcium ion channel activity / presynaptic active zone membrane / somatodendritic compartment / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / synaptic membrane / dendritic shaft / regulation of membrane potential / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / response to cocaine / calcium channel regulator activity / synaptic transmission, glutamatergic / PDZ domain binding / neuromuscular junction / response to nutrient levels / postsynaptic density membrane / cerebral cortex development / calcium channel activity / receptor internalization / small GTPase binding / Schaffer collateral - CA1 synapse / long-term synaptic potentiation / recycling endosome membrane / synaptic vesicle / synaptic vesicle membrane / cell-cell junction / G-protein beta-subunit binding / response to estradiol / presynapse / amyloid-beta binding / cell body / scaffold protein binding / early endosome membrane / response to ethanol / chemical synaptic transmission / dendritic spine / postsynaptic membrane / neuron projection / postsynapse 類似検索 - 分子機能 Voltage-dependent calcium channel, gamma-8 subunit / Cornichon / Cornichon, conserved site / Cornichon protein / Cornichon family signature. / Cornichon / : / PMP-22/EMP/MP20/Claudin family / Voltage-dependent calcium channel, gamma subunit / PMP-22/EMP/MP20/Claudin superfamily ... Voltage-dependent calcium channel, gamma-8 subunit / Cornichon / Cornichon, conserved site / Cornichon protein / Cornichon family signature. / Cornichon / : / PMP-22/EMP/MP20/Claudin family / Voltage-dependent calcium channel, gamma subunit / PMP-22/EMP/MP20/Claudin superfamily / Ionotropic glutamate receptor, metazoa / Ligated ion channel L-glutamate- and glycine-binding site / Ionotropic glutamate receptor, L-glutamate and glycine-binding domain / Ligated ion channel L-glutamate- and glycine-binding site / Ligand-gated ion channel / : / Ionotropic glutamate receptor / Eukaryotic homologues of bacterial periplasmic substrate binding proteins. / Receptor, ligand binding region / Receptor family ligand binding region / Periplasmic binding protein-like I 類似検索 - ドメイン・相同性 Glutamate receptor / Protein cornichon homolog 2 / Glutamate receptor 1 / Voltage-dependent calcium channel gamma-8 subunit 類似検索 - 構成要素生物種 Mus musculus (ハツカネズミ)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.9 Å 詳細 データ登録者Yu J / Rao P 資金援助 米国, 1件 詳細 詳細を隠すOrganization Grant number 国 National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS) R01NS038631 米国
引用ジャーナル : Nature / 年 : 2021タイトル : Hippocampal AMPA receptor assemblies and mechanism of allosteric inhibition.著者 : Jie Yu / Prashant Rao / Sarah Clark / Jaba Mitra / Taekjip Ha / Eric Gouaux / 要旨 : AMPA-selective glutamate receptors mediate the transduction of signals between the neuronal circuits of the hippocampus. The trafficking, localization, kinetics and pharmacology of AMPA receptors are ... AMPA-selective glutamate receptors mediate the transduction of signals between the neuronal circuits of the hippocampus. The trafficking, localization, kinetics and pharmacology of AMPA receptors are tuned by an ensemble of auxiliary protein subunits, which are integral membrane proteins that associate with the receptor to yield bona fide receptor signalling complexes. Thus far, extensive studies of recombinant AMPA receptor-auxiliary subunit complexes using engineered protein constructs have not been able to faithfully elucidate the molecular architecture of hippocampal AMPA receptor complexes. Here we obtain mouse hippocampal, calcium-impermeable AMPA receptor complexes using immunoaffinity purification and use single-molecule fluorescence and cryo-electron microscopy experiments to elucidate three major AMPA receptor-auxiliary subunit complexes. The GluA1-GluA2, GluA1-GluA2-GluA3 and GluA2-GluA3 receptors are the predominant assemblies, with the auxiliary subunits TARP-γ8 and CNIH2-SynDIG4 non-stochastically positioned at the B'/D' and A'/C' positions, respectively. We further demonstrate how the receptor-TARP-γ8 stoichiometry explains the mechanism of and submaximal inhibition by a clinically relevant, brain-region-specific allosteric inhibitor. 履歴 登録 2021年1月13日 - ヘッダ(付随情報) 公開 2021年5月12日 - マップ公開 2021年5月12日 - 更新 2024年10月9日 - 現状 2024年10月9日 処理サイト : RCSB / 状態 : 公開
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