+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6cvj | ||||||
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タイトル | Model of synthetic tau (four tandem repeats of first repeat sequence) bound to the microtubule | ||||||
要素 |
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キーワード | STRUCTURAL PROTEIN / microtubule / tau | ||||||
機能・相同性 | 機能・相同性情報 Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane / Hedgehog 'off' state / Cilium Assembly / Intraflagellar transport / COPI-dependent Golgi-to-ER retrograde traffic / Carboxyterminal post-translational modifications of tubulin / RHOH GTPase cycle / Sealing of the nuclear envelope (NE) by ESCRT-III / Kinesins / PKR-mediated signaling ...Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane / Hedgehog 'off' state / Cilium Assembly / Intraflagellar transport / COPI-dependent Golgi-to-ER retrograde traffic / Carboxyterminal post-translational modifications of tubulin / RHOH GTPase cycle / Sealing of the nuclear envelope (NE) by ESCRT-III / Kinesins / PKR-mediated signaling / The role of GTSE1 in G2/M progression after G2 checkpoint / Aggrephagy / Resolution of Sister Chromatid Cohesion / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / Separation of Sister Chromatids / RHO GTPases activate IQGAPs / RHO GTPases Activate Formins / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / MHC class II antigen presentation / Recruitment of NuMA to mitotic centrosomes / COPI-mediated anterograde transport / plus-end-directed organelle transport along microtubule / histone-dependent DNA binding / neurofibrillary tangle assembly / positive regulation of diacylglycerol kinase activity / axonal transport / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / positive regulation of protein localization to synapse / microtubule lateral binding / tubulin complex / phosphatidylinositol bisphosphate binding / main axon / negative regulation of kinase activity / regulation of long-term synaptic depression / negative regulation of tubulin deacetylation / generation of neurons / rRNA metabolic process / internal protein amino acid acetylation / regulation of chromosome organization / regulation of mitochondrial fission / axonal transport of mitochondrion / intracellular distribution of mitochondria / axon development / central nervous system neuron development / regulation of microtubule polymerization / apolipoprotein binding / microtubule polymerization / lipoprotein particle binding / minor groove of adenine-thymine-rich DNA binding / dynactin binding / glial cell projection / negative regulation of mitochondrial membrane potential / protein polymerization / axolemma / negative regulation of mitochondrial fission / Caspase-mediated cleavage of cytoskeletal proteins / regulation of microtubule polymerization or depolymerization / positive regulation of axon extension / regulation of microtubule cytoskeleton organization / Activation of AMPK downstream of NMDARs / regulation of cellular response to heat / positive regulation of protein localization / cytoplasmic microtubule organization / stress granule assembly / supramolecular fiber organization / regulation of calcium-mediated signaling / axon cytoplasm / somatodendritic compartment / positive regulation of microtubule polymerization / synapse assembly / cellular response to brain-derived neurotrophic factor stimulus / phosphatidylinositol binding / nuclear periphery / cellular response to nerve growth factor stimulus / positive regulation of superoxide anion generation / protein phosphatase 2A binding / regulation of autophagy / astrocyte activation / response to lead ion / microglial cell activation / synapse organization / Hsp90 protein binding / protein homooligomerization / PKR-mediated signaling / regulation of synaptic plasticity / structural constituent of cytoskeleton / : / memory / SH3 domain binding / microtubule cytoskeleton organization / cytoplasmic ribonucleoprotein granule / cellular response to reactive oxygen species / microtubule cytoskeleton / neuron projection development / 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 / cell-cell signaling / single-stranded DNA binding / mitotic cell cycle 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) Sus scrofa (ブタ) | ||||||
手法 | 電子顕微鏡法 / らせん対称体再構成法 / クライオ電子顕微鏡法 / 解像度: 3.2 Å | ||||||
データ登録者 | Nogales, E. / Kellogg, E.H. | ||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Science / 年: 2018 タイトル: Near-atomic model of microtubule-tau interactions. 著者: Elizabeth H Kellogg / Nisreen M A Hejab / Simon Poepsel / Kenneth H Downing / Frank DiMaio / Eva Nogales / 要旨: Tau is a developmentally regulated axonal protein that stabilizes and bundles microtubules (MTs). Its hyperphosphorylation is thought to cause detachment from MTs and subsequent aggregation into ...Tau is a developmentally regulated axonal protein that stabilizes and bundles microtubules (MTs). Its hyperphosphorylation is thought to cause detachment from MTs and subsequent aggregation into fibrils implicated in Alzheimer's disease. It is unclear which tau residues are crucial for tau-MT interactions, where tau binds on MTs, and how it stabilizes them. We used cryo-electron microscopy to visualize different tau constructs on MTs and computational approaches to generate atomic models of tau-tubulin interactions. The conserved tubulin-binding repeats within tau adopt similar extended structures along the crest of the protofilament, stabilizing the interface between tubulin dimers. Our structures explain the effect of phosphorylation on MT affinity and lead to a model of tau repeats binding in tandem along protofilaments, tethering together tubulin dimers and stabilizing polymerization interfaces. | ||||||
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 | 6cvj.cif.gz | 240 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6cvj.ent.gz | 182.9 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6cvj.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
文書・要旨 | 6cvj_validation.pdf.gz | 1.1 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 6cvj_full_validation.pdf.gz | 1.1 MB | 表示 | |
XML形式データ | 6cvj_validation.xml.gz | 42.4 KB | 表示 | |
CIF形式データ | 6cvj_validation.cif.gz | 62.5 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/cv/6cvj ftp://data.pdbj.org/pub/pdb/validation_reports/cv/6cvj | HTTPS FTP |
-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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2 |
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3 |
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対称性 | らせん対称: (回転対称性: 1 / Dyad axis: no / N subunits divisor: 1 / Num. of operations: 30 / Rise per n subunits: 8.65 Å / Rotation per n subunits: -25.75 °) |
-要素
-タンパク質 , 3種, 4分子 ABCD
#1: タンパク質 | 分子量: 50204.445 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Sus scrofa (ブタ) / 参照: UniProt: Q2XVP4 | ||
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#2: タンパク質 | 分子量: 49907.770 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) Sus scrofa (ブタ) / 参照: UniProt: P02554 #3: タンパク質 | | 分子量: 21903.201 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P10636*PLUS |
-非ポリマー , 3種, 4分子
#4: 化合物 | ChemComp-GTP / |
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#5: 化合物 | ChemComp-MG / |
#6: 化合物 |
-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: FILAMENT / 3次元再構成法: らせん対称体再構成法 |
-試料調製
構成要素 |
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分子量 | 実験値: NO | ||||||||||||||||||||||||||||||
由来(天然) |
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由来(組換発現) | 生物種: Escherichia coli (大腸菌) | ||||||||||||||||||||||||||||||
緩衝液 | pH: 6.8 | ||||||||||||||||||||||||||||||
緩衝液成分 |
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試料 | 濃度: 0.5 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES 詳細: tubulin concentration is 0.5 mg/mL, tau concentration is 1 mg/mL | ||||||||||||||||||||||||||||||
試料支持 | グリッドの材料: COPPER / グリッドのサイズ: 400 divisions/in. / グリッドのタイプ: C-flat-1.2/1.3 4C | ||||||||||||||||||||||||||||||
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 310.15 K 詳細: blot force 10 pN, 6 second blot time. used C-flat 1.2/1.3 holey grids. First 2 uL of microtubules were adhered to grid for 30 seconds, followed by 2 4 uL washes of tau with 30 second incubation for each wash |
-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 / 倍率(公称値): 35714 X / 最大 デフォーカス(公称値): 2500 nm / 最小 デフォーカス(公称値): 1000 nm / Cs: 2.7 mm / C2レンズ絞り径: 100 µm / アライメント法: COMA FREE |
試料ホルダ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | 平均露光時間: 7.5 sec. / 電子線照射量: 45 e/Å2 / 検出モード: SUPER-RESOLUTION フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 撮影したグリッド数: 1 / 実像数: 712 |
画像スキャン | 動画フレーム数/画像: 30 |
-解析
EMソフトウェア |
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画像処理 | 詳細: used motioncorr2 to correct for beam-induced motion | ||||||||||||||||||||||||||||||||
CTF補正 | タイプ: PHASE FLIPPING ONLY | ||||||||||||||||||||||||||||||||
らせん対称 | 回転角度/サブユニット: -25.75 ° / 軸方向距離/サブユニット: 8.65 Å / らせん対称軸の対称性: C1 | ||||||||||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 57526 | ||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3.2 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 40522 / アルゴリズム: FOURIER SPACE / 対称性のタイプ: HELICAL | ||||||||||||||||||||||||||||||||
原子モデル構築 | B value: 120 / プロトコル: FLEXIBLE FIT / 空間: REAL / Target criteria: real space correlation |