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基本情報
登録情報 | データベース: EMDB / ID: EMD-4564 | |||||||||
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タイトル | Cryo-EM reconstruction of heparin-induced 2N4R tau twister filaments | |||||||||
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機能・相同性 | ![]() 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 ...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 / regulation of long-term synaptic depression / negative regulation of kinase activity / negative regulation of tubulin deacetylation / generation of neurons / positive regulation of protein localization / 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 / microtubule polymerization / minor groove of adenine-thymine-rich DNA binding / lipoprotein particle binding / dynactin binding / glial cell projection / apolipoprotein binding / 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 / supramolecular fiber organization / cytoplasmic microtubule organization / regulation of cellular response to heat / stress granule assembly / regulation of calcium-mediated signaling / axon cytoplasm / positive regulation of microtubule polymerization / somatodendritic compartment / 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 / synapse organization / microglial cell activation / Hsp90 protein binding / regulation of synaptic plasticity / PKR-mediated signaling / protein homooligomerization / memory / microtubule cytoskeleton organization / SH3 domain binding / cellular response to reactive oxygen species / cytoplasmic ribonucleoprotein granule / activation of cysteine-type endopeptidase activity involved in apoptotic process / microtubule cytoskeleton / neuron projection development / cell-cell signaling / protein-macromolecule adaptor activity / actin binding / single-stranded DNA binding / protein-folding chaperone binding / cellular response to heat / cell body / growth cone / microtubule binding / double-stranded DNA binding / microtubule / amyloid fibril formation / sequence-specific DNA binding / dendritic spine / learning or memory / nuclear speck / neuron projection / membrane raft / axon / negative regulation of gene expression / neuronal cell body / dendrite / DNA damage response / protein kinase binding / enzyme binding / mitochondrion / DNA binding 類似検索 - 分子機能 | |||||||||
生物種 | ![]() | |||||||||
手法 | らせん対称体再構成法 / クライオ電子顕微鏡法 / 解像度: 3.3 Å | |||||||||
![]() | Zhang W / Falcon B / Murzin AG / Fan J / Crowther RA / Goedert M / Scheres SHW | |||||||||
![]() | ![]() タイトル: Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer's and Pick's diseases. 著者: Wenjuan Zhang / Benjamin Falcon / Alexey G Murzin / Juan Fan / R Anthony Crowther / Michel Goedert / Sjors Hw Scheres / ![]() 要旨: Assembly of microtubule-associated protein tau into filamentous inclusions underlies a range of neurodegenerative diseases. Tau filaments adopt different conformations in Alzheimer's and Pick's ...Assembly of microtubule-associated protein tau into filamentous inclusions underlies a range of neurodegenerative diseases. Tau filaments adopt different conformations in Alzheimer's and Pick's diseases. Here, we used cryo- and immuno- electron microscopy to characterise filaments that were assembled from recombinant full-length human tau with four (2N4R) or three (2N3R) microtubule-binding repeats in the presence of heparin. 2N4R tau assembles into multiple types of filaments, and the structures of three types reveal similar 'kinked hairpin' folds, in which the second and third repeats pack against each other. 2N3R tau filaments are structurally homogeneous, and adopt a dimeric core, where the third repeats of two tau molecules pack in a parallel manner. The heparin-induced tau filaments differ from those of Alzheimer's or Pick's disease, which have larger cores with different repeat compositions. Our results illustrate the structural versatility of amyloid filaments, and raise questions about the relevance of in vitro assembly. | |||||||||
履歴 |
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構造の表示
ムービー |
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構造ビューア | EMマップ: ![]() ![]() ![]() |
添付画像 |
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ダウンロードとリンク
-EMDBアーカイブ
マップデータ | ![]() | 12.4 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 18.8 KB 18.8 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 9.1 KB | 表示 | ![]() |
画像 | ![]() | 24.9 KB | ||
マスクデータ | ![]() | 64 MB | ![]() | |
その他 | ![]() ![]() | 48.7 MB 48.7 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 6qjmMC ![]() 4563C ![]() 4565C ![]() 4566C ![]() 6qjhC ![]() 6qjpC ![]() 6qjqC M: このマップから作成された原子モデル C: 同じ文献を引用 ( |
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類似構造データ | |
電子顕微鏡画像生データ | ![]() Data size: 446.3 / Data #1: Aligned micrographs [micrographs - single frame] / Data #2: Raw movies [micrographs - multiframe]) |
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リンク
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | None | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.38 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-マスク #1
ファイル | ![]() | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Half map of helical reconstruction of heparin-induced 2N4R...
ファイル | emd_4564_half_map_1.map | ||||||||||||
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注釈 | Half map of helical reconstruction of heparin-induced 2N4R tau twister filaments | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: The other half map of helical reconstruction of...
ファイル | emd_4564_half_map_2.map | ||||||||||||
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注釈 | The other half map of helical reconstruction of heparin-induced 2N4R tau twister filaments | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
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試料の構成要素
-全体 : heparin-induced 2N4R tau twister filaments
全体 | 名称: heparin-induced 2N4R tau twister filaments |
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要素 |
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-超分子 #1: heparin-induced 2N4R tau twister filaments
超分子 | 名称: heparin-induced 2N4R tau twister filaments / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all 詳細: Recombinant 2N4R tau protein was induced into filaments by adding heparin |
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由来(天然) | 生物種: ![]() |
組換発現 | 生物種: ![]() ![]() |
分子量 | 理論値: 45.85 kDa/nm |
-分子 #1: Isoform Tau-F of Microtubule-associated protein tau
分子 | 名称: Isoform Tau-F of Microtubule-associated protein tau / タイプ: other / ID: 1 / 分類: other |
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由来(天然) | 生物種: ![]() |
配列 | 文字列: MAEPRQEFEV MEDHAGTYGL GDRKDQGGYT MHQDQEGDTD AGLKESPLQT PTEDGSEEPG SETSDAKST PTAEDVTAPL VDEGAPGKQA AAQPHTEIPE GTTAEEAGIG DTPSLEDEAA G HVTQARMV SKSKDGTGSD DKKAKGADGK TKIATPRGAA PPGQKGQANA ...文字列: MAEPRQEFEV MEDHAGTYGL GDRKDQGGYT MHQDQEGDTD AGLKESPLQT PTEDGSEEPG SETSDAKST PTAEDVTAPL VDEGAPGKQA AAQPHTEIPE GTTAEEAGIG DTPSLEDEAA G HVTQARMV SKSKDGTGSD DKKAKGADGK TKIATPRGAA PPGQKGQANA TRIPAKTPPA PK TPPSSGE PPKSGDRSGY SSPGSPGTPG SRSRTPSLPT PPTREPKKVA VVRTPPKSPS SAK SRLQTA PVPMPDLKNV KSKIGSTENL KHQPGGGKVQ IINKKLDLSN VQSKCGSKDN IKHV PGGGS VQIVYKPVDL SKVTSKCGSL GNIHHKPGGG QVEVKSEKLD FKDRVQSKIG SLDNI THVP GGGNKKIETH KLTFRENAKA KTDHGAEIVY KSPVVSGDTS PRHLSNVSST GSIDMV DSP QLATLADEVS ASLAKQGL |
組換発現 | 生物種: ![]() ![]() |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | らせん対称体再構成法 |
試料の集合状態 | filament |
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試料調製
濃度 | 2.0 mg/mL | |||||||||
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緩衝液 | pH: 7.4 構成要素:
詳細: 20 mM Tris, pH 7.4, 100mM NaCl | |||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 277 K / 装置: FEI VITROBOT MARK IV / 詳細: Blot force: -12 ; Blot time: 4s. | |||||||||
詳細 | Recombinant tau protein was induced into filaments by incubation with heparin at 37 degree celsius for 3 days |
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電子顕微鏡法
顕微鏡 | FEI POLARA 300 |
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撮影 | フィルム・検出器のモデル: FEI FALCON III (4k x 4k) 検出モード: INTEGRATING / デジタル化 - サイズ - 横: 4096 pixel / デジタル化 - サイズ - 縦: 4096 pixel / デジタル化 - サンプリング間隔: 14.0 µm / 撮影したグリッド数: 1 / 実像数: 717 / 平均露光時間: 1.0 sec. / 平均電子線量: 48.0 e/Å2 詳細: Images were collected in movie-mode at 30 frames per second |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | C2レンズ絞り径: 50.0 µm / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.0 mm / 最大 デフォーカス(公称値): 2.8 µm / 最小 デフォーカス(公称値): 1.7 µm |
試料ステージ | 試料ホルダーモデル: GATAN LIQUID NITROGEN / ホルダー冷却材: NITROGEN |
実験機器 | ![]() モデル: Tecnai Polara / 画像提供: FEI Company |
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画像解析
-原子モデル構築 1
詳細 | A stack of three consecutive monomers was refined to preserve nearest-neighbour interactions for the middle chain. Side-chain clashes were detected using MOLPROBITY, and corrected by iterative cycles of real-space refinement in COOT and Fourier-space refinement in REFMAC and PHENIX. For each refined structure, separate model refinements were performed against a single half-map, and the resulting model was compared to the other half-map to confirm the absence of overfitting. |
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精密化 | 空間: RECIPROCAL / プロトコル: AB INITIO MODEL / 温度因子: 58.51 / 当てはまり具合の基準: Fourier shell correlation |
得られたモデル | ![]() PDB-6qjm: |