+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-16953 | ||||||||||||||||||
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タイトル | MurineArc type I Abeta fibril from tg-APPArcSwe mouse | ||||||||||||||||||
マップデータ | Ex vivo Abeta fibril from tg-APPArcSwe mouse brain. | ||||||||||||||||||
試料 |
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キーワード | Amyloid fibril / PROTEIN FIBRIL | ||||||||||||||||||
機能・相同性 | 機能・相同性情報 regulation of epidermal growth factor-activated receptor activity / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / regulation of Wnt signaling pathway / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / synaptic assembly at neuromuscular junction / signaling receptor activator activity ...regulation of epidermal growth factor-activated receptor activity / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / regulation of Wnt signaling pathway / Formyl peptide receptors bind formyl peptides and many other ligands / axo-dendritic transport / synaptic assembly at neuromuscular junction / signaling receptor activator activity / axon midline choice point recognition / smooth endoplasmic reticulum calcium ion homeostasis / astrocyte activation involved in immune response / regulation of spontaneous synaptic transmission / mating behavior / NMDA selective glutamate receptor signaling pathway / ciliary rootlet / Lysosome Vesicle Biogenesis / PTB domain binding / Golgi-associated vesicle / neuron remodeling / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / positive regulation of amyloid fibril formation / positive regulation of G2/M transition of mitotic cell cycle / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / nuclear envelope lumen / COPII-coated ER to Golgi transport vesicle / suckling behavior / dendrite development / presynaptic active zone / modulation of excitatory postsynaptic potential / regulation of peptidyl-tyrosine phosphorylation / TRAF6 mediated NF-kB activation / Advanced glycosylation endproduct receptor signaling / neuromuscular process controlling balance / The NLRP3 inflammasome / regulation of presynapse assembly / transition metal ion binding / negative regulation of long-term synaptic potentiation / regulation of multicellular organism growth / negative regulation of neuron differentiation / ECM proteoglycans / intracellular copper ion homeostasis / smooth endoplasmic reticulum / positive regulation of T cell migration / spindle midzone / Purinergic signaling in leishmaniasis infection / protein serine/threonine kinase binding / positive regulation of chemokine production / clathrin-coated pit / forebrain development / Notch signaling pathway / neuron projection maintenance / positive regulation of protein metabolic process / positive regulation of calcium-mediated signaling / astrocyte activation / ionotropic glutamate receptor signaling pathway / positive regulation of glycolytic process / response to interleukin-1 / cholesterol metabolic process / positive regulation of mitotic cell cycle / extracellular matrix organization / adult locomotory behavior / axonogenesis / platelet alpha granule lumen / trans-Golgi network membrane / positive regulation of peptidyl-threonine phosphorylation / positive regulation of interleukin-1 beta production / learning / dendritic shaft / positive regulation of long-term synaptic potentiation / Mitochondrial protein degradation / central nervous system development / locomotory behavior / endosome lumen / positive regulation of JNK cascade / Post-translational protein phosphorylation / synapse organization / microglial cell activation / regulation of long-term neuronal synaptic plasticity / TAK1-dependent IKK and NF-kappa-B activation / visual learning / neuromuscular junction / positive regulation of non-canonical NF-kappaB signal transduction / recycling endosome / cognition / G2/M transition of mitotic cell cycle / Golgi lumen / positive regulation of inflammatory response / neuron cellular homeostasis / positive regulation of interleukin-6 production / cellular response to amyloid-beta / endocytosis / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / serine-type endopeptidase inhibitor activity / positive regulation of peptidyl-serine phosphorylation / positive regulation of tumor necrosis factor production / neuron projection development / cell-cell junction / synaptic vesicle 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 | Zielinski M / Peralta Reyes FS / Gremer L / Schemmert S / Frieg B / Willuweit A / Donner L / Elvers M / Nilsson LNG / Syvanen S ...Zielinski M / Peralta Reyes FS / Gremer L / Schemmert S / Frieg B / Willuweit A / Donner L / Elvers M / Nilsson LNG / Syvanen S / Sehlin D / Ingelsson M / Willbold D / Schroeder GF | ||||||||||||||||||
資金援助 | ドイツ, スウェーデン, 5件
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引用 | ジャーナル: Nat Neurosci / 年: 2023 タイトル: Cryo-EM of Aβ fibrils from mouse models find tg-APP fibrils resemble those found in patients with sporadic Alzheimer's disease. 著者: Mara Zielinski / Fernanda S Peralta Reyes / Lothar Gremer / Sarah Schemmert / Benedikt Frieg / Luisa U Schäfer / Antje Willuweit / Lili Donner / Margitta Elvers / Lars N G Nilsson / Stina ...著者: Mara Zielinski / Fernanda S Peralta Reyes / Lothar Gremer / Sarah Schemmert / Benedikt Frieg / Luisa U Schäfer / Antje Willuweit / Lili Donner / Margitta Elvers / Lars N G Nilsson / Stina Syvänen / Dag Sehlin / Martin Ingelsson / Dieter Willbold / Gunnar F Schröder / 要旨: The use of transgenic mice displaying amyloid-β (Aβ) brain pathology has been essential for the preclinical assessment of new treatment strategies for Alzheimer's disease. However, the properties ...The use of transgenic mice displaying amyloid-β (Aβ) brain pathology has been essential for the preclinical assessment of new treatment strategies for Alzheimer's disease. However, the properties of Aβ in such mice have not been systematically compared to Aβ in the brains of patients with Alzheimer's disease. Here, we determined the structures of nine ex vivo Aβ fibrils from six different mouse models by cryogenic-electron microscopy. We found novel Aβ fibril structures in the APP/PS1, ARTE10 and tg-SwDI models, whereas the human type II filament fold was found in the ARTE10, tg-APP and APP23 models. The tg-APP mice showed an Aβ fibril whose structure resembles the human type I filament found in patients with sporadic Alzheimer's disease. A detailed assessment of the Aβ fibril structure is key to the selection of adequate mouse models for the preclinical development of novel plaque-targeting therapeutics and positron emission tomography imaging tracers in Alzheimer's disease. | ||||||||||||||||||
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_16953.map.gz | 9.3 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-16953-v30.xml emd-16953.xml | 15.7 KB 15.7 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_16953_fsc.xml | 9.1 KB | 表示 | FSCデータファイル |
画像 | emd_16953.png | 38.5 KB | ||
Filedesc metadata | emd-16953.cif.gz | 5.3 KB | ||
その他 | emd_16953_half_map_1.map.gz emd_16953_half_map_2.map.gz | 49.6 MB 49.6 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-16953 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-16953 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_16953_validation.pdf.gz | 190.3 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_16953_full_validation.pdf.gz | 189.9 KB | 表示 | |
XML形式データ | emd_16953_validation.xml.gz | 501 B | 表示 | |
CIF形式データ | emd_16953_validation.cif.gz | 373 B | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-16953 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-16953 | HTTPS FTP |
-関連構造データ
関連構造データ | 8ol7MC 8ol2C 8ol3C 8ol5C 8ol6C 8olgC 8olnC 8oloC 8olqC 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_16953.map.gz / 形式: CCP4 / 大きさ: 64 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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注釈 | Ex vivo Abeta fibril from tg-APPArcSwe mouse brain. | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.808 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: Ex vivo Abeta fibril from tg-APPArcSwe mouse brain. Half map 1.
ファイル | emd_16953_half_map_1.map | ||||||||||||
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注釈 | Ex vivo Abeta fibril from tg-APPArcSwe mouse brain. Half map 1. | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Ex vivo Abeta fibril from tg-APPArcSwe mouse brain. Half map 2.
ファイル | emd_16953_half_map_2.map | ||||||||||||
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注釈 | Ex vivo Abeta fibril from tg-APPArcSwe mouse brain. Half map 2. | ||||||||||||
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 : Amyloid fibril of amyloid-beta
全体 | 名称: Amyloid fibril of amyloid-beta |
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要素 |
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-超分子 #1: Amyloid fibril of amyloid-beta
超分子 | 名称: Amyloid fibril of amyloid-beta / 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) |
分子量 | 理論値: 20 kDa/nm |
-分子 #1: Amyloid-beta protein 42
分子 | 名称: Amyloid-beta protein 42 / タイプ: protein_or_peptide / ID: 1 / コピー数: 10 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) / 器官: Brain |
分子量 | 理論値: 4.448025 KDa |
組換発現 | 生物種: Mus musculus (ハツカネズミ) |
配列 | 文字列: DAEFRHDSGY EVHHQKLVFF AGDVGSNKGA IIGLMVGGVV IA UniProtKB: Amyloid-beta precursor protein |
-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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凍結 | 凍結剤: ETHANE / 装置: FEI VITROBOT MARK IV |
-電子顕微鏡法
顕微鏡 | TFS KRIOS |
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撮影 | フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) 撮影したグリッド数: 1 / 実像数: 17577 / 平均電子線量: 40.35 e/Å2 |
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 FIELD / 最大 デフォーカス(公称値): 3.0 µm / 最小 デフォーカス(公称値): 0.5 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |