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