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 / negative regulation of receptor localization to synapse / negative regulation of anterograde synaptic vesicle transport / Synaptic adhesion-like molecules / Cargo concentration in the ER / Unblocking of NMDA receptors, glutamate binding and activation / COPII-mediated vesicle transport / LGI-ADAM interactions ... Phase 0 - rapid depolarisation / Phase 2 - plateau phase / Activation of AMPA receptors / negative regulation of receptor localization to synapse / negative regulation of anterograde synaptic vesicle transport / Synaptic adhesion-like molecules / Cargo concentration in the ER / Unblocking of NMDA receptors, glutamate binding and activation / COPII-mediated vesicle transport / LGI-ADAM interactions / cellular response to amine stimulus / axonal spine / Trafficking of GluR2-containing AMPA receptors / Trafficking of AMPA receptors / positive regulation of membrane potential / localization within membrane / cellular response to ammonium ion / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / neurotransmitter receptor transport, postsynaptic endosome to lysosome / L-type voltage-gated calcium channel complex / myosin V binding / neuron spine / cellular response to dsRNA / regulation of AMPA receptor activity / neurotransmitter receptor internalization / protein phosphatase 2B binding / response to arsenic-containing substance / postsynaptic neurotransmitter receptor diffusion trapping / nervous system process / dendritic spine membrane / long-term synaptic depression / beta-2 adrenergic receptor binding / cellular response to peptide hormone stimulus / protein kinase A binding / spinal cord development / neuronal cell body membrane / perisynaptic space / AMPA glutamate receptor activity / transmission of nerve impulse / channel regulator activity / response to lithium ion / immunoglobulin binding / regulation of postsynaptic membrane neurotransmitter receptor levels / AMPA glutamate receptor complex / excitatory synapse / adenylate cyclase binding / ionotropic glutamate receptor complex / regulation of postsynaptic membrane potential / asymmetric synapse / postsynaptic density, intracellular component / calcium channel regulator activity / regulation of receptor recycling / neuronal action potential / G-protein alpha-subunit binding / voltage-gated calcium channel activity / glutamate receptor binding / positive regulation of synaptic transmission / response to electrical stimulus / long-term memory / glutamate-gated receptor activity / response to fungicide / glutamate-gated calcium ion channel activity / presynaptic active zone membrane / vesicle-mediated transport / ionotropic glutamate receptor binding / somatodendritic compartment / dendrite membrane / synapse assembly / cellular response to brain-derived neurotrophic factor stimulus / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / positive regulation of synaptic transmission, glutamatergic / regulation of membrane potential / dendritic shaft / response to cocaine / synaptic transmission, glutamatergic / synaptic membrane / long-term synaptic potentiation / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / PDZ domain binding / cellular response to amino acid stimulus / postsynaptic density membrane / modulation of chemical synaptic transmission / neuromuscular junction / regulation of synaptic plasticity / Schaffer collateral - CA1 synapse / receptor internalization / cerebral cortex development / response to toxic substance / small GTPase binding / synaptic vesicle membrane / recycling endosome membrane / G-protein beta-subunit binding / cell-cell junction / synaptic vesicle / response to estradiol / presynapse / presynaptic membrane / amyloid-beta binding / early endosome membrane / cell body 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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