+データを開く
-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 | ||||||
要素 |
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キーワード | 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 | 機能・相同性情報 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 / COPII-mediated vesicle transport / LGI-ADAM interactions ...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 / 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 transport, postsynaptic endosome to lysosome / L-type voltage-gated calcium channel complex / myosin V binding / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / 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 / anchoring junction / 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 / transmission of nerve impulse / AMPA glutamate receptor activity / channel regulator activity / response to lithium ion / regulation of postsynaptic membrane neurotransmitter receptor levels / immunoglobulin binding / AMPA glutamate receptor complex / adenylate cyclase binding / ionotropic glutamate receptor complex / excitatory synapse / neuronal action potential / 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 / postsynaptic density, intracellular component / positive regulation of synaptic transmission / glutamate receptor binding / long-term memory / response to electrical stimulus / glutamate-gated receptor activity / glutamate-gated calcium ion channel activity / presynaptic active zone membrane / response to fungicide / vesicle-mediated transport / 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 / ionotropic glutamate receptor binding / positive regulation of synaptic transmission, glutamatergic / regulation of membrane potential / response to cocaine / dendritic shaft / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / synaptic membrane / synaptic transmission, glutamatergic / PDZ domain binding / long-term synaptic potentiation / 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 / response to toxic substance / cerebral cortex development / 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 | ||||||
生物種 | Mus musculus (ハツカネズミ) | ||||||
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 | ||||||
データ登録者 | Yu, J. / Rao, P. / Gouaux, E. | ||||||
資金援助 | 米国, 1件
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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. #1: ジャーナル: Science / 年: 2019 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. | ||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7ldd.cif.gz | 830.5 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7ldd.ent.gz | 658.4 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7ldd.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/ld/7ldd ftp://data.pdbj.org/pub/pdb/validation_reports/ld/7ldd | HTTPS FTP |
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-関連構造データ
-リンク
-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) Mus musculus (ハツカネズミ) / 参照: UniProt: P23818 #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) Mus musculus (ハツカネズミ) / 参照: UniProt: G5E8H1 #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) Mus musculus (ハツカネズミ) / 参照: UniProt: O35089 #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) Mus musculus (ハツカネズミ) / 参照: UniProt: Q8VHW2 |
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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) Mus musculus (ハツカネズミ) / 発現宿主: Escherichia coli (大腸菌) #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) Mus musculus (ハツカネズミ) 発現宿主: Spodoptera aff. frugiperda 1 BOLD-2017 (蝶・蛾) #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) Mus musculus (ハツカネズミ) 発現宿主: Spodoptera aff. frugiperda 1 BOLD-2017 (蝶・蛾) |
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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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-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 |
-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 |
-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: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
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) |
-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 |