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基本情報
登録情報 | データベース: PDB / ID: 7lde | ||||||
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タイトル | native AMPA receptor | ||||||
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![]() | MEMBRANE PROTEIN / neurotransmitter / hippocampus / ion-channel / glycosylation | ||||||
機能・相同性 | ![]() Phase 2 - plateau phase / Activation of AMPA receptors / Phase 0 - rapid depolarisation / 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 / LGI-ADAM interactions / COPII-mediated vesicle transport ...Phase 2 - plateau phase / Activation of AMPA receptors / Phase 0 - rapid depolarisation / 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 / LGI-ADAM interactions / COPII-mediated vesicle transport / Trafficking of AMPA receptors / cellular response to amine stimulus / axonal spine / Trafficking of GluR2-containing AMPA receptors / 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 / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / myosin V binding / neuron spine / regulation of AMPA receptor activity / neurotransmitter receptor internalization / channel regulator activity / protein phosphatase 2B binding / response to arsenic-containing substance / cellular response to dsRNA / postsynaptic neurotransmitter receptor diffusion trapping / dendritic spine membrane / glutamate-gated calcium ion channel activity / anchoring junction / long-term synaptic depression / cellular response to peptide hormone stimulus / protein kinase A binding / spinal cord development / neuronal cell body membrane / perisynaptic space / transmission of nerve impulse / AMPA glutamate receptor activity / COPII-coated ER to Golgi transport vesicle / regulation of postsynaptic membrane neurotransmitter receptor levels / response to lithium ion / immunoglobulin binding / AMPA glutamate receptor complex / adenylate cyclase binding / ionotropic glutamate receptor complex / excitatory synapse / calcium channel regulator activity / asymmetric synapse / G-protein alpha-subunit binding / regulation of receptor recycling / voltage-gated calcium channel activity / neuronal action potential / regulation of postsynaptic membrane potential / postsynaptic density, intracellular component / glutamate receptor binding / positive regulation of synaptic transmission / long-term memory / endoplasmic reticulum to Golgi vesicle-mediated transport / response to electrical stimulus / glutamate-gated receptor activity / presynaptic active zone membrane / beta-2 adrenergic receptor binding / response to fungicide / somatodendritic compartment / cellular response to brain-derived neurotrophic factor stimulus / dendrite membrane / synapse assembly / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / positive regulation of synaptic transmission, glutamatergic / response to cocaine / dendritic shaft / synaptic membrane / synaptic transmission, glutamatergic / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / PDZ domain binding / regulation of membrane potential / long-term synaptic potentiation / cellular response to amino acid stimulus / postsynaptic density membrane / ionotropic glutamate receptor binding / Schaffer collateral - CA1 synapse / modulation of chemical synaptic transmission / regulation of synaptic plasticity / neuromuscular junction / receptor internalization / response to toxic substance / cerebral cortex development / synaptic vesicle membrane / small GTPase binding / recycling endosome membrane / G-protein beta-subunit binding / cell-cell junction / synaptic vesicle / presynapse / response to estradiol / presynaptic membrane / amyloid-beta binding / early endosome membrane 類似検索 - 分子機能 | ||||||
生物種 | ![]() ![]() | ||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.9 Å | ||||||
![]() | Yu, J. / Rao, P. / Gouaux, E. | ||||||
資金援助 | ![]()
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![]() | ![]() 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. | ||||||
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構造の表示
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構造ビューア | 分子: ![]() ![]() |
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ダウンロード
PDBx/mmCIF形式 | ![]() | 831.7 KB | 表示 | ![]() |
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PDB形式 | ![]() | 657.7 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
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-検証レポート
文書・要旨 | ![]() | 1.6 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.6 MB | 表示 | |
XML形式データ | ![]() | 121 KB | 表示 | |
CIF形式データ | ![]() | 185.3 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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リンク
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集合体
登録構造単位 | ![]()
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要素
-タンパク質 , 4種, 8分子 ACBDEFGH
#1: タンパク質 | 分子量: 101678.969 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() #2: タンパク質 | 分子量: 98899.883 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() #3: タンパク質 | 分子量: 18948.420 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() #4: タンパク質 | 分子量: 43502.938 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() |
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-抗体 , 3種, 6分子 ILJMKN
#5: 抗体 | 分子量: 27511.527 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() ![]() #6: 抗体 | 分子量: 25111.660 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() 発現宿主: ![]() #7: 抗体 | 分子量: 27975.439 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() 発現宿主: ![]() |
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-糖 , 2種, 12分子 ![](data/chem/img/NAG.gif)
#8: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #14: 糖 | ChemComp-NAG / |
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-非ポリマー , 9種, 40分子 ![](data/chem/img/ZK1.gif)
![](data/chem/img/R16.gif)
![](data/chem/img/OCT.gif)
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![](data/chem/img/D10.gif)
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![](data/chem/img/XVD.gif)
![](data/chem/img/R16.gif)
![](data/chem/img/OCT.gif)
![](data/chem/img/HP6.gif)
![](data/chem/img/D10.gif)
![](data/chem/img/D12.gif)
![](data/chem/img/C14.gif)
![](data/chem/img/DD9.gif)
![](data/chem/img/XVD.gif)
#9: 化合物 | ChemComp-ZK1 / {[ #10: 化合物 | #11: 化合物 | ChemComp-OCT / #12: 化合物 | ChemComp-HP6 / #13: 化合物 | ChemComp-D10 / #15: 化合物 | ChemComp-D12 / #16: 化合物 | ChemComp-C14 / #17: 化合物 | ChemComp-DD9 / #18: 化合物 | |
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-詳細
研究の焦点であるリガンドがあるか | Y |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
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試料調製
構成要素 |
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由来(天然) |
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由来(組換発現) |
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緩衝液 | pH: 8 | ||||||||||||||||||||||||||||||
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||||||||||||||||||||
急速凍結 | 凍結剤: ETHANE |
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電子顕微鏡撮影
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 50 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
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解析
ソフトウェア | 名称: PHENIX / バージョン: 1.17_3644: / 分類: 精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 157000 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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