登録情報 データベース : EMDB / ID : EMD-12805 構造の表示 ダウンロードとリンクタイトル Resting state GluA1/A2 AMPA receptor in complex with TARP gamma 8 and CNIH2 (LBD-TMD) マップデータComposite map generated based on masked refinement maps of LBD and TMD. 詳細 試料複合体 : GluA1/A2 heterotetramer in complex with auxiliary subunits TARP gamma 8 and CNIH2タンパク質・ペプチド : Glutamate receptor 1タンパク質・ペプチド : Glutamate receptor 2タンパク質・ペプチド : Protein cornichon homolog 2タンパク質・ペプチド : Voltage-dependent calcium channel gamma-8 subunitリガンド : 6-nitro-2,3-bis(oxidanylidene)-1,4-dihydrobenzo[f]quinoxaline-7-sulfonamideリガンド : 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINEリガンド : CHOLESTEROL 詳細機能・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 2 - plateau phase / Phase 0 - rapid depolarisation / Cargo concentration in the ER / cellular response to amine stimulus / axonal spine / COPII-mediated vesicle transport / positive regulation of membrane potential / localization within membrane ... negative regulation of receptor localization to synapse / negative regulation of anterograde synaptic vesicle transport / Phase 2 - plateau phase / Phase 0 - rapid depolarisation / Cargo concentration in the ER / cellular response to amine stimulus / axonal spine / COPII-mediated vesicle transport / positive regulation of membrane potential / localization within membrane / cellular response to ammonium ion / neurotransmitter receptor transport, postsynaptic endosome to lysosome / L-type voltage-gated calcium channel complex / LGI-ADAM interactions / myosin V binding / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / Trafficking of AMPA receptors / neuron spine / regulation of AMPA receptor activity / protein phosphatase 2B binding / neurotransmitter receptor internalization / response to arsenic-containing substance / cellular response to dsRNA / postsynaptic neurotransmitter receptor diffusion trapping / dendritic spine membrane / regulation of NMDA receptor activity / Synaptic adhesion-like molecules / long-term synaptic depression / cellular response to peptide hormone stimulus / protein kinase A binding / spinal cord development / spine synapse / dendritic spine neck / neuronal cell body membrane / dendritic spine head / Activation of AMPA receptors / perisynaptic space / transmission of nerve impulse / AMPA glutamate receptor activity / channel regulator activity / ligand-gated monoatomic cation channel activity / Trafficking of GluR2-containing AMPA receptors / regulation of postsynaptic membrane neurotransmitter receptor levels / response to lithium ion / immunoglobulin binding / AMPA glutamate receptor complex / adenylate cyclase binding / kainate selective glutamate receptor activity / cellular response to organic cyclic compound / ionotropic glutamate receptor complex / excitatory synapse / extracellularly glutamate-gated ion channel activity / neuronal action potential / cellular response to glycine / calcium channel regulator activity / asymmetric synapse / G-protein alpha-subunit binding / regulation of receptor recycling / voltage-gated calcium channel activity / regulation of postsynaptic membrane potential / Unblocking of NMDA receptors, glutamate binding and activation / postsynaptic density, intracellular component / positive regulation of synaptic transmission / glutamate receptor binding / long-term memory / extracellular ligand-gated monoatomic ion channel activity / beta-2 adrenergic receptor binding / response to electrical stimulus / glutamate-gated calcium ion channel activity / glutamate-gated receptor activity / presynaptic active zone membrane / response to fungicide / vesicle-mediated transport / regulation of synaptic transmission, glutamatergic / somatodendritic compartment / synapse assembly / cellular response to brain-derived neurotrophic factor stimulus / dendrite membrane / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / cytoskeletal protein binding / dendrite cytoplasm / ionotropic glutamate receptor signaling pathway / positive regulation of synaptic transmission, glutamatergic / SNARE binding / regulation of membrane potential / response to cocaine / dendritic shaft / synaptic membrane / synaptic transmission, glutamatergic / PDZ domain binding / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / long-term synaptic potentiation / protein tetramerization / cellular response to amino acid stimulus / postsynaptic density membrane / ionotropic glutamate receptor binding / modulation of chemical synaptic transmission / establishment of protein localization / neuromuscular junction / regulation of synaptic plasticity 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 / Bacterial extracellular solute-binding proteins, family 3 / Solute-binding protein family 3/N-terminal domain of MltF / 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 1 / Glutamate receptor 2 / Protein cornichon homolog 2 / Voltage-dependent calcium channel gamma-8 subunit 類似検索 - 構成要素生物種 Rattus norvegicus (ドブネズミ)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.1 Å 詳細 データ登録者Zhang D / Watson JF / Matthews PM / Cais O / Greger IH 資金援助 2件 詳細 詳細を隠すOrganization Grant number 国 Medical Research Council (MRC, United Kingdom) MC_U105174197 Biotechnology and Biological Sciences Research Council (BBSRC) BB/N002113/1
引用ジャーナル : Nature / 年 : 2021タイトル : Gating and modulation of a hetero-octameric AMPA glutamate receptor.著者 : Danyang Zhang / Jake F Watson / Peter M Matthews / Ondrej Cais / Ingo H Greger / 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. 履歴 登録 2021年4月26日 - ヘッダ(付随情報) 公開 2021年6月9日 - マップ公開 2021年6月9日 - 更新 2021年6月30日 - 現状 2021年6月30日 処理サイト : PDBe / 状態 : 公開
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