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基本情報
登録情報 | データベース: PDB / ID: 7ldd | ||||||
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タイトル | native AMPA receptor | ||||||
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![]() | MEMBRANE PROTEIN/IMMUNE SYSTEM / neurotransmitter / two-fold symmetry / hippocampus / ion-channel / MEMBRANE PROTEIN / SIGNALING PROTEIN-IMMUNE SYSTEM complex / MEMBRANE PROTEIN-IMMUNE SYSTEM complex | ||||||
機能・相同性 | ![]() 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 / channel regulator activity / regulation of AMPA receptor 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 / calcium channel regulator activity / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / response to cocaine / 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 | ||||||
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: 3.4 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. #1: ![]() タイトル: Architecture and subunit arrangement of native AMPA receptors elucidated by cryo-EM. 著者: Yan Zhao / Shanshuang Chen / Adam C Swensen / Wei-Jun Qian / Eric Gouaux / ![]() 要旨: Glutamate-gated AMPA receptors mediate the fast component of excitatory signal transduction at chemical synapses throughout all regions of the mammalian brain. AMPA receptors are tetrameric ...Glutamate-gated AMPA receptors mediate the fast component of excitatory signal transduction at chemical synapses throughout all regions of the mammalian brain. AMPA receptors are tetrameric assemblies composed of four subunits, GluA1-GluA4. Despite decades of study, the subunit composition, subunit arrangement, and molecular structure of native AMPA receptors remain unknown. Here we elucidate the structures of 10 distinct native AMPA receptor complexes by single-particle cryo-electron microscopy (cryo-EM). We find that receptor subunits are arranged nonstochastically, with the GluA2 subunit preferentially occupying the B and D positions of the tetramer and with triheteromeric assemblies comprising a major population of native AMPA receptors. Cryo-EM maps define the structure for S2-M4 linkers between the ligand-binding and transmembrane domains, suggesting how neurotransmitter binding is coupled to ion channel gating. | ||||||
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構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 839.8 KB | 表示 | ![]() |
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PDB形式 | ![]() | 647.5 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 | ![]() | 1.7 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.8 MB | 表示 | |
XML形式データ | ![]() | 122 KB | 表示 | |
CIF形式データ | ![]() | 187.2 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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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 
#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 
















#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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Has protein modification | Y |
-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
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3次元再構成 | 解像度: 3.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 829000 / 対称性のタイプ: POINT |