+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-18990 | |||||||||||||||
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タイトル | CryoEM map of tau PHF sarkosyl-extracted from a human AD patient (associated with in situ tomography) | |||||||||||||||
マップデータ | Postprocessed sharpened map of tau PHF fibrils extracted from AD patient brain | |||||||||||||||
試料 |
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キーワード | Amyloid / Alzheimer's / tauopathy / fibril / filament / helical / PROTEIN FIBRIL | |||||||||||||||
機能・相同性 | 機能・相同性情報 plus-end-directed organelle transport along microtubule / axonal transport / 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 / axonal transport / 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 / positive regulation of protein localization / regulation of chromosome organization / 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 / microtubule polymerization / minor groove of adenine-thymine-rich DNA binding / lipoprotein particle binding / dynactin binding / apolipoprotein binding / glial cell projection / negative regulation of mitochondrial membrane potential / 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 / regulation of microtubule cytoskeleton organization / Activation of AMPK downstream of NMDARs / supramolecular fiber organization / regulation of cellular response to heat / stress granule assembly / cytoplasmic microtubule organization / regulation of calcium-mediated signaling / axon cytoplasm / positive regulation of microtubule polymerization / 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 / memory / cytoplasmic ribonucleoprotein granule / SH3 domain binding / microtubule cytoskeleton organization / cellular response to reactive oxygen species / activation of cysteine-type endopeptidase activity involved in apoptotic process / neuron projection development / microtubule cytoskeleton / cell-cell signaling / protein-macromolecule adaptor activity / actin binding / cellular response to heat / single-stranded DNA binding / protein-folding chaperone binding / 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 / DNA damage response / dendrite / protein kinase binding / enzyme binding / mitochondrion / DNA binding 類似検索 - 分子機能 | |||||||||||||||
生物種 | 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: 3.0 Å | |||||||||||||||
データ登録者 | Wilkinson MW / Gilbert MAG / Fatima N / Jenkins J / O'Sullivan TJ / Schertel A / Halfon Y / Morrema THJ / Geibel M / Ranson NA ...Wilkinson MW / Gilbert MAG / Fatima N / Jenkins J / O'Sullivan TJ / Schertel A / Halfon Y / Morrema THJ / Geibel M / Ranson NA / Radford SE / Hoozemans JJM / Frank RAW | |||||||||||||||
資金援助 | 英国, 4件
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引用 | ジャーナル: Nature / 年: 2024 タイトル: CryoET of β-amyloid and tau within postmortem Alzheimer's disease brain. 著者: Madeleine A G Gilbert / Nayab Fatima / Joshua Jenkins / Thomas J O'Sullivan / Andreas Schertel / Yehuda Halfon / Martin Wilkinson / Tjado H J Morrema / Mirjam Geibel / Randy J Read / Neil A ...著者: Madeleine A G Gilbert / Nayab Fatima / Joshua Jenkins / Thomas J O'Sullivan / Andreas Schertel / Yehuda Halfon / Martin Wilkinson / Tjado H J Morrema / Mirjam Geibel / Randy J Read / Neil A Ranson / Sheena E Radford / Jeroen J M Hoozemans / René A W Frank / 要旨: A defining pathological feature of most neurodegenerative diseases is the assembly of proteins into amyloid that form disease-specific structures. In Alzheimer's disease, this is characterized by the ...A defining pathological feature of most neurodegenerative diseases is the assembly of proteins into amyloid that form disease-specific structures. In Alzheimer's disease, this is characterized by the deposition of β-amyloid and tau with disease-specific conformations. The in situ structure of amyloid in the human brain is unknown. Here, using cryo-fluorescence microscopy-targeted cryo-sectioning, cryo-focused ion beam-scanning electron microscopy lift-out and cryo-electron tomography, we determined in-tissue architectures of β-amyloid and tau pathology in a postmortem Alzheimer's disease donor brain. β-amyloid plaques contained a mixture of fibrils, some of which were branched, and protofilaments, arranged in parallel arrays and lattice-like structures. Extracellular vesicles and cuboidal particles defined the non-amyloid constituents of β-amyloid plaques. By contrast, tau inclusions formed parallel clusters of unbranched filaments. Subtomogram averaging a cluster of 136 tau filaments in a single tomogram revealed the polypeptide backbone conformation and filament polarity orientation of paired helical filaments within tissue. Filaments within most clusters were similar to each other, but were different between clusters, showing amyloid heterogeneity that is spatially organized by subcellular location. The in situ structural approaches outlined here for human donor tissues have applications to a broad range of neurodegenerative diseases. | |||||||||||||||
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_18990.map.gz | 38.9 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-18990-v30.xml emd-18990.xml | 18.6 KB 18.6 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_18990_fsc.xml | 11.9 KB | 表示 | FSCデータファイル |
画像 | emd_18990.png | 93.5 KB | ||
Filedesc metadata | emd-18990.cif.gz | 5.9 KB | ||
その他 | emd_18990_half_map_1.map.gz emd_18990_half_map_2.map.gz | 114 MB 114 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-18990 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-18990 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_18990_validation.pdf.gz | 1000.7 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_18990_full_validation.pdf.gz | 1000.2 KB | 表示 | |
XML形式データ | emd_18990_validation.xml.gz | 19.5 KB | 表示 | |
CIF形式データ | emd_18990_validation.cif.gz | 25.7 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-18990 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-18990 | HTTPS FTP |
-関連構造データ
関連構造データ | 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_18990.map.gz / 形式: CCP4 / 大きさ: 144.7 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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注釈 | Postprocessed sharpened map of tau PHF fibrils extracted from AD patient brain | ||||||||||||||||||||||||||||||||||||
投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.83 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
-ハーフマップ: halfmap1
ファイル | emd_18990_half_map_1.map | ||||||||||||
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注釈 | halfmap1 | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: halfmap2
ファイル | emd_18990_half_map_2.map | ||||||||||||
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注釈 | halfmap2 | ||||||||||||
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 : tau PHF amyloid fibril
全体 | 名称: tau PHF amyloid fibril |
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要素 |
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-超分子 #1: tau PHF amyloid fibril
超分子 | 名称: tau PHF amyloid fibril / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
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由来(天然) | 生物種: Homo sapiens (ヒト) / 器官: Brain |
-分子 #1: Microtubule-associated protein tau
分子 | 名称: Microtubule-associated protein tau / タイプ: protein_or_peptide / ID: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) / 器官: Brain |
配列 | 文字列: MAEPRQEFEV MEDHAGTYGL GDRKDQGGYT MHQDQEGDTD AGLKESPLQT PTEDGSEEPG SETSDAKST PTAEDVTAPL VDEGAPGKQA AAQPHTEIPE GTTAEEAGIG DTPSLEDEAA G HVTQEPES GKVVQEGFLR EPGPPGLSHQ LMSGMPGAPL LPEGPREATR ...文字列: MAEPRQEFEV MEDHAGTYGL GDRKDQGGYT MHQDQEGDTD AGLKESPLQT PTEDGSEEPG SETSDAKST PTAEDVTAPL VDEGAPGKQA AAQPHTEIPE GTTAEEAGIG DTPSLEDEAA G HVTQEPES GKVVQEGFLR EPGPPGLSHQ LMSGMPGAPL LPEGPREATR QPSGTGPEDT EG GRHAPEL LKHQLLGDLH QEGPPLKGAG GKERPGSKEE VDEDRDVDES SPQDSPPSKA SPA QDGRPP QTAAREATSI PGFPAEGAIP LPVDFLSKVS TEIPASEPDG PSVGRAKGQD APLE FTFHV EITPNVQKEQ AHSEEHLGRA AFPGAPGEGP EARGPSLGED TKEADLPEPS EKQPA AAPR GKPVSRVPQL KARMVSKSKD GTGSDDKKAK TSTRSSAKTL KNRPCLSPKH PTPGSS DPL IQPSSPAVCP EPPSSPKYVS SVTSRTGSSG AKEMKLKGAD GKTKIATPRG AAPPGQK GQ ANATRIPAKT PPAPKTPPSS GEPPKSGDRS GYSSPGSPGT PGSRSRTPSL PTPPTREP K KVAVVRTPPK SPSSAKSRLQ TAPVPMPDLK NVKSKIGSTE NLKHQPGGGK VQIINKKLD LSNVQSKCGS KDNIKHVPGG GSVQIVYKPV DLSKVTSKCG SLGNIHHKPG GGQVEVKSEK LDFKDRVQS KIGSLDNITH VPGGGNKKIE THKLTFRENA KAKTDHGAEI VYKSPVVSGD T SPRHLSNV SSTGSIDMVD SPQLATLADE VSASLAKQGL UniProtKB: Microtubule-associated protein tau |
-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 / 構成要素:
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グリッド | モデル: Quantifoil R1.2/1.3 / 材質: COPPER / メッシュ: 300 / 前処理 - タイプ: PLASMA CLEANING / 前処理 - 時間: 60 sec. | |||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 90 % / チャンバー内温度: 279 K / 装置: FEI VITROBOT MARK IV | |||||||||
詳細 | Frozen brain section was homogenised and purified using sarkosyl detergent. |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) デジタル化 - サイズ - 横: 4096 pixel / デジタル化 - サイズ - 縦: 4096 pixel / 撮影したグリッド数: 1 / 実像数: 10860 / 平均露光時間: 4.0 sec. / 平均電子線量: 44.0 e/Å2 詳細: Each EER movie was fractionated and tif compressed into 38 frames with a dose of 1.16 e-/A2/frame prior to processing |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
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: 2.7 mm / 最大 デフォーカス(公称値): 2.7 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 | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |