+データを開く
-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) | |||||||||
要素 |
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キーワード | MEMBRANE PROTEIN / AMPAR / ion channels / neurotransmission | |||||||||
機能・相同性 | 機能・相同性情報 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 / beta-2 adrenergic receptor binding / 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 / response to lithium ion / regulation of postsynaptic membrane neurotransmitter receptor levels / 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 / positive regulation of synaptic transmission, glutamatergic / response to electrical stimulus / glutamate-gated receptor activity / glutamate-gated calcium ion channel 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 / ionotropic glutamate receptor binding / dendrite cytoplasm / ionotropic glutamate receptor signaling pathway / cellular response to amino acid stimulus / regulation of membrane potential / SNARE binding / response to cocaine / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential / dendritic shaft / synaptic membrane / synaptic transmission, glutamatergic / PDZ domain binding / long-term synaptic potentiation / protein tetramerization / postsynaptic density membrane / modulation of chemical synaptic transmission / establishment of protein localization / neuromuscular junction / regulation of synaptic plasticity 類似検索 - 分子機能 | |||||||||
生物種 | Rattus norvegicus (ドブネズミ) | |||||||||
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: 3.6 Å | |||||||||
データ登録者 | Zhang, D. / Watson, J.F. / Matthews, P.M. / Cais, O. / Greger, I.H. | |||||||||
資金援助 | 2件
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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 |
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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 | 7ocf.cif.gz | 445.7 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7ocf.ent.gz | 334.9 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7ocf.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/oc/7ocf ftp://data.pdbj.org/pub/pdb/validation_reports/oc/7ocf | 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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1 |
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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) Rattus norvegicus (ドブネズミ) / 遺伝子: Gria1, Glur1 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P19490 #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) Rattus norvegicus (ドブネズミ) / 遺伝子: Gria2, Glur2 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P19491 |
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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) Rattus norvegicus (ドブネズミ) / 遺伝子: Cnih2 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q5BJU5 #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) Rattus norvegicus (ドブネズミ) / 遺伝子: Cacng8 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q8VHW5 |
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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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-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 | 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: Rattus norvegicus (ドブネズミ) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) |
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 |
-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 / 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) |
-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 |
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