+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-18268 | |||||||||
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タイトル | P301S Tau Filaments from the Brains of PS19 Transgenic Mouse Line | |||||||||
マップデータ | ||||||||||
試料 |
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キーワード | P301S tau / Frontotemporal dementia and parkinsonism linked to chromosome 17 / Transgenic mice / Electron cryo-microscopy (低温電子顕微鏡法) / PROTEIN FIBRIL | |||||||||
機能・相同性 | 機能・相同性情報 plus-end-directed organelle transport along microtubule / 軸索輸送 / histone-dependent DNA binding / neurofibrillary tangle assembly / positive regulation of diacylglycerol kinase activity / 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 / 軸索輸送 / histone-dependent DNA binding / neurofibrillary tangle assembly / positive regulation of diacylglycerol kinase activity / 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 / regulation of chromosome organization / positive regulation of protein localization / rRNA metabolic process / internal protein amino acid acetylation / regulation of mitochondrial fission / intracellular distribution of mitochondria / axonal transport of mitochondrion / axon development / central nervous system neuron development / regulation of microtubule polymerization / 微小管 / minor groove of adenine-thymine-rich DNA binding / lipoprotein particle binding / dynactin binding / glial cell projection / negative regulation of mitochondrial membrane potential / apolipoprotein binding / protein polymerization / negative regulation of mitochondrial fission / axolemma / Caspase-mediated cleavage of cytoskeletal proteins / regulation of microtubule polymerization or depolymerization / positive regulation of axon extension / Activation of AMPK downstream of NMDARs / regulation of microtubule cytoskeleton organization / supramolecular fiber organization / stress granule assembly / regulation of cellular response to heat / cytoplasmic microtubule organization / regulation of calcium-mediated signaling / positive regulation of microtubule polymerization / axon cytoplasm / somatodendritic compartment / cellular response to brain-derived neurotrophic factor stimulus / synapse assembly / 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 / 記憶 / cellular response to reactive oxygen species / microtubule cytoskeleton organization / SH3 domain binding / cytoplasmic ribonucleoprotein granule / activation of cysteine-type endopeptidase activity involved in apoptotic process / neuron projection development / microtubule cytoskeleton / cell-cell signaling / protein-macromolecule adaptor activity / actin binding / single-stranded DNA binding / cellular response to heat / cell body / protein-folding chaperone binding / 成長円錐 / microtubule binding / double-stranded DNA binding / 微小管 / sequence-specific DNA binding / amyloid fibril formation / 樹状突起スパイン / learning or memory / nuclear speck / neuron projection / 脂質ラフト / 神経繊維 / negative regulation of gene expression / neuronal cell body / DNA damage response / 樹状突起 / protein kinase binding / enzyme binding / ミトコンドリア / DNA binding 類似検索 - 分子機能 | |||||||||
生物種 | Mus musculus (ハツカネズミ) / Homo sapiens (ヒト) | |||||||||
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: 3.05 Å | |||||||||
データ登録者 | Schweighauser M / Murzin AG / Macdonald J / Lavenir I / Crowther RA / Scheres SHW / Goedert M | |||||||||
資金援助 | 英国, 2件
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引用 | ジャーナル: Acta Neuropathol Commun / 年: 2023 タイトル: Cryo-EM structures of tau filaments from the brains of mice transgenic for human mutant P301S Tau. 著者: Manuel Schweighauser / Alexey G Murzin / Jennifer Macdonald / Isabelle Lavenir / R Anthony Crowther / Sjors H W Scheres / Michel Goedert / 要旨: Mice transgenic for human mutant P301S tau are widely used as models for human tauopathies. They develop neurodegeneration and abundant filamentous inclusions made of human mutant four-repeat tau. ...Mice transgenic for human mutant P301S tau are widely used as models for human tauopathies. They develop neurodegeneration and abundant filamentous inclusions made of human mutant four-repeat tau. Here we used electron cryo-microscopy (cryo-EM) to determine the structures of tau filaments from the brains of Tg2541 and PS19 mice. Both lines express human P301S tau (0N4R for Tg2541 and 1N4R for PS19) on mixed genetic backgrounds and downstream of different promoters (murine Thy1 for Tg2541 and murine Prnp for PS19). The structures of tau filaments from Tg2541 and PS19 mice differ from each other and those of wild-type tau filaments from human brains. The structures of tau filaments from the brains of humans with mutations P301L, P301S or P301T in MAPT are not known. Filaments from the brains of Tg2541 and PS19 mice share a substructure at the junction of repeats 2 and 3, which comprises residues I297-V312 of tau and includes the P301S mutation. The filament core from the brainstem of Tg2541 mice consists of residues K274-H329 of tau and two disconnected protein densities. Two non-proteinaceous densities are also in evidence. The filament core from the cerebral cortex of line PS19 extends from residues G271-P364 of tau. One strong non-proteinaceous density is also present. Unlike the tau filaments from human brains, the sequences following repeat 4 are missing from the cores of tau filaments from the brains of Tg2541 and PS19 mice. | |||||||||
履歴 |
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-構造の表示
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 | emd_18268.map.gz | 77.2 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-18268-v30.xml emd-18268.xml | 15.2 KB 15.2 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_18268_fsc.xml | 15.6 KB | 表示 | FSCデータファイル |
画像 | emd_18268.png | 25.7 KB | ||
マスクデータ | emd_18268_msk_1.map | 325 MB | マスクマップ | |
Filedesc metadata | emd-18268.cif.gz | 5.4 KB | ||
その他 | emd_18268_half_map_1.map.gz emd_18268_half_map_2.map.gz | 259.4 MB 259.8 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-18268 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-18268 | HTTPS FTP |
-関連構造データ
関連構造データ | 8q92MC 8q96C 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 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_18268.map.gz / 形式: CCP4 / 大きさ: 325 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 0.824 Å | ||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-マスク #1
ファイル | emd_18268_msk_1.map | ||||||||||||
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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: #2
ファイル | emd_18268_half_map_1.map | ||||||||||||
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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: #1
ファイル | emd_18268_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : P301S Tau Protein Filament (PS19)
全体 | 名称: P301S Tau Protein Filament (PS19) |
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要素 |
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-超分子 #1: P301S Tau Protein Filament (PS19)
超分子 | 名称: P301S Tau Protein Filament (PS19) / タイプ: tissue / ID: 1 / 親要素: 0 / 含まれる分子: all 詳細: Human P301S tau filaments extracted from the brains of transgenic mouse line PS19 |
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由来(天然) | 生物種: Mus musculus (ハツカネズミ) / 株: PS19 / 器官: Brain / 組織: Cerebral Cortex |
-分子 #1: Microtubule-associated protein tau
分子 | 名称: Microtubule-associated protein tau / タイプ: protein_or_peptide / ID: 1 / コピー数: 3 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) / 株: Transgenic PS19 / 器官: Brain / 組織: Cerebral Cortex |
分子量 | 理論値: 9.96743 KDa |
組換発現 | 生物種: Mus musculus (ハツカネズミ) |
配列 | 文字列: GGGKVQIINK KLDLSNVQSK CGSKDNIKHV SGGGSVQIVY KPVDLSKVTS KCGSLGNIHH KPGGGQVEVK SEKLDFKDRV QSKIGSLDN ITHVP UniProtKB: タウタンパク質 |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | らせん対称体再構成法 |
試料の集合状態 | filament |
-試料調製
緩衝液 | pH: 7.4 |
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グリッド | モデル: Quantifoil R1.2/1.3 / 材質: GOLD / メッシュ: 300 / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 60 sec. |
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 |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELDBright-field microscopy / 最大 デフォーカス(公称値): 2.4 µm / 最小 デフォーカス(公称値): 1.5 µm / 倍率(公称値): 96000 |
試料ステージ | ホルダー冷却材: NITROGEN |
撮影 | フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) 平均電子線量: 30.0 e/Å2 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |