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基本情報
登録情報 | データベース: PDB / ID: 7ocf | |||||||||
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タイトル | Active state GluA1/A2 AMPA receptor in complex with TARP gamma 8 and CNIH2 (LBD-TMD) | |||||||||
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![]() | MEMBRANE PROTEIN / AMPAR / ion channels / neurotransmission | |||||||||
機能・相同性 | ![]() negative regulation of receptor localization to synapse / negative regulation of anterograde synaptic vesicle transport / Phase 0 - rapid depolarisation / Phase 2 - plateau phase / Cargo concentration in the ER / cellular response to amine stimulus / axonal spine / COPII-mediated vesicle transport / positive regulation of membrane potential / positive regulation of locomotion involved in locomotory behavior ...negative regulation of receptor localization to synapse / negative regulation of anterograde synaptic vesicle transport / Phase 0 - rapid depolarisation / Phase 2 - plateau phase / Cargo concentration in the ER / cellular response to amine stimulus / axonal spine / COPII-mediated vesicle transport / positive regulation of membrane potential / positive regulation of locomotion involved in locomotory behavior / localization within membrane / cellular response to ammonium ion / response to sucrose / L-type voltage-gated calcium channel complex / LGI-ADAM interactions / postsynaptic neurotransmitter receptor diffusion trapping / neuron spine / myosin V binding / Trafficking of AMPA receptors / channel regulator activity / proximal dendrite / regulation of monoatomic ion transmembrane transport / protein phosphatase 2B binding / regulation of AMPA receptor activity / cellular response to L-glutamate / response to arsenic-containing substance / regulation of NMDA receptor activity / conditioned place preference / cellular response to dsRNA / dendritic spine membrane / long-term synaptic depression / Synaptic adhesion-like molecules / beta-2 adrenergic receptor binding / response to morphine / cellular response to peptide hormone stimulus / neuronal cell body membrane / spine synapse / dendritic spine neck / protein kinase A binding / dendritic spine head / peptide hormone receptor binding / response to psychosocial stress / spinal cord development / Activation of AMPA receptors / perisynaptic space / ligand-gated monoatomic cation channel activity / AMPA glutamate receptor activity / transmission of nerve impulse / Trafficking of GluR2-containing AMPA receptors / response to lithium ion / behavioral response to pain / kainate selective glutamate receptor activity / AMPA glutamate receptor complex / cellular response to glycine / extracellularly glutamate-gated ion channel activity / adenylate cyclase binding / ionotropic glutamate receptor complex / asymmetric synapse / immunoglobulin binding / excitatory synapse / positive regulation of excitatory postsynaptic potential / response to electrical stimulus / regulation of receptor recycling / G-protein alpha-subunit binding / long-term memory / Unblocking of NMDA receptors, glutamate binding and activation / glutamate receptor binding / positive regulation of synaptic transmission / regulation of postsynaptic membrane neurotransmitter receptor levels / postsynaptic density, intracellular component / voltage-gated calcium channel activity / neuronal action potential / response to fungicide / regulation of synaptic transmission, glutamatergic / glutamate-gated receptor activity / cytoskeletal protein binding / synapse assembly / vesicle-mediated transport / presynaptic active zone membrane / extracellular ligand-gated monoatomic ion channel activity / cellular response to brain-derived neurotrophic factor stimulus / glutamate-gated calcium ion channel activity / somatodendritic compartment / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / ionotropic glutamate receptor binding / dendrite membrane / calcium channel regulator activity / ionotropic glutamate receptor signaling pathway / dendrite cytoplasm / positive regulation of synaptic transmission, glutamatergic / SNARE binding / dendritic shaft / regulation of membrane potential / PDZ domain binding / response to nutrient levels / synaptic transmission, glutamatergic / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / protein tetramerization / cellular response to amino acid stimulus / response to cocaine 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: 3.6 Å | |||||||||
![]() | Zhang, D. / Watson, J.F. / Matthews, P.M. / Cais, O. / Greger, I.H. | |||||||||
資金援助 | 2件
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![]() | ![]() 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. | |||||||||
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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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PDBx/mmCIF形式 | ![]() | 453.1 KB | 表示 | ![]() |
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PDB形式 | ![]() | 326.2 KB | 表示 | ![]() |
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-検証レポート
文書・要旨 | ![]() | 1.9 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.9 MB | 表示 | |
XML形式データ | ![]() | 75.7 KB | 表示 | |
CIF形式データ | ![]() | 107.5 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
-Isoform Flip of Glutamate receptor ... , 2種, 4分子 ACBD
#1: タンパク質 | 分子量: 102661.930 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() #2: タンパク質 | 分子量: 96247.055 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() |
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-タンパク質 , 2種, 4分子 GEIJ
#3: タンパク質 | 分子量: 22000.605 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() #4: タンパク質 | 分子量: 43576.004 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() |
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-非ポリマー , 3種, 34分子 




#5: 化合物 | ChemComp-CYZ / #6: 化合物 | ChemComp-PC1 / #7: 化合物 | ChemComp-GLU / |
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-詳細
研究の焦点であるリガンドがあるか | N |
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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 | 名称: GluA1/A2 heterotetramer in complex with auxiliary subunits TARP gamma 8 and CNIH2 タイプ: COMPLEX / Entity ID: #1-#4 / 由来: RECOMBINANT |
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分子量 | 値: 0.527 MDa / 実験値: NO |
由来(天然) | 生物種: ![]() ![]() |
由来(組換発現) | 生物種: ![]() |
緩衝液 | pH: 8 |
試料 | 濃度: 3 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES 詳細: Purified protein was first incubated with 300 uM cyclothiazide (CTZ) for at least 30 min on ice and then quickly mixed with 1 M L-glutamate stock solution to 100 mM final L-Glu concentration ...詳細: Purified protein was first incubated with 300 uM cyclothiazide (CTZ) for at least 30 min on ice and then quickly mixed with 1 M L-glutamate stock solution to 100 mM final L-Glu concentration just before being loaded onto the grids. |
試料支持 | グリッドの材料: COPPER / グリッドのサイズ: 300 divisions/in. / グリッドのタイプ: Quantifoil R1.2/1.3 |
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 / アライメント法: COMA FREE |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
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
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
対称性 | 点対称性: C2 (2回回転対称) | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.6 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 120052 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
原子モデル構築 | プロトコル: RIGID BODY FIT / 空間: REAL | ||||||||||||||||||||||||
原子モデル構築 | 3D fitting-ID: 1 / Source name: PDB / タイプ: experimental model
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