+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-16022 | |||||||||
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タイトル | Amyloid-beta 42 filaments extracted from the human brain with Arctic mutation (E22G) of Alzheimer's disease | ABeta42 | |||||||||
マップデータ | ||||||||||
試料 |
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キーワード | Amyloid / filaments / amyloid-beta / Arctic mutation / APP / E22G / E693G / 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 / smooth endoplasmic reticulum calcium ion homeostasis / axon midline choice point recognition / 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 / positive regulation of amyloid fibril formation / neuron remodeling / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / nuclear envelope lumen / suckling behavior / COPII-coated ER to Golgi transport vesicle / dendrite development / presynaptic active zone / modulation of excitatory postsynaptic potential / 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 / intracellular copper ion homeostasis / negative regulation of neuron differentiation / ECM proteoglycans / smooth endoplasmic reticulum / positive regulation of T cell migration / spindle midzone / Purinergic signaling in leishmaniasis infection / positive regulation of calcium-mediated signaling / protein serine/threonine kinase binding / positive regulation of chemokine production / clathrin-coated pit / regulation of peptidyl-tyrosine phosphorylation / forebrain development / Notch signaling pathway / Mitochondrial protein degradation / neuron projection maintenance / positive regulation of G2/M transition of mitotic cell cycle / positive regulation of protein metabolic process / positive regulation of glycolytic process / ionotropic glutamate receptor signaling pathway / 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 / central nervous system development / locomotory behavior / endosome lumen / astrocyte activation / positive regulation of JNK cascade / Post-translational protein phosphorylation / microglial cell activation / synapse organization / regulation of long-term neuronal synaptic plasticity / TAK1-dependent IKK and NF-kappa-B activation / serine-type endopeptidase inhibitor activity / visual learning / neuromuscular junction / recycling endosome / cognition / Golgi lumen / positive regulation of inflammatory response / neuron cellular homeostasis / positive regulation of non-canonical NF-kappaB signal transduction / endocytosis / cellular response to amyloid-beta / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / positive regulation of interleukin-6 production / G2/M transition of mitotic cell cycle / positive regulation of tumor necrosis factor production / neuron projection development / cell-cell junction / synaptic vesicle / Platelet degranulation 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: 2.8 Å | |||||||||
データ登録者 | Yang Y / Zhang WJ / Murzin AG / Schweighauser M / Huang M / Lovestam SKA / Peak-Chew SY / Macdonald J / Lavenir I / Ghetti B ...Yang Y / Zhang WJ / Murzin AG / Schweighauser M / Huang M / Lovestam SKA / Peak-Chew SY / Macdonald J / Lavenir I / Ghetti B / Graff C / Kumar A / Nordberg A / Goedert M / Scheres SHW | |||||||||
資金援助 | 英国, 2件
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引用 | ジャーナル: Acta Neuropathol / 年: 2023 タイトル: Cryo-EM structures of amyloid-β filaments with the Arctic mutation (E22G) from human and mouse brains. 著者: Yang Yang / Wenjuan Zhang / Alexey G Murzin / Manuel Schweighauser / Melissa Huang / Sofia Lövestam / Sew Y Peak-Chew / Takashi Saito / Takaomi C Saido / Jennifer Macdonald / Isabelle ...著者: Yang Yang / Wenjuan Zhang / Alexey G Murzin / Manuel Schweighauser / Melissa Huang / Sofia Lövestam / Sew Y Peak-Chew / Takashi Saito / Takaomi C Saido / Jennifer Macdonald / Isabelle Lavenir / Bernardino Ghetti / Caroline Graff / Amit Kumar / Agneta Nordberg / Michel Goedert / Sjors H W Scheres / 要旨: The Arctic mutation, encoding E693G in the amyloid precursor protein (APP) gene [E22G in amyloid-β (Aβ)], causes dominantly inherited Alzheimer's disease. Here, we report the high-resolution cryo- ...The Arctic mutation, encoding E693G in the amyloid precursor protein (APP) gene [E22G in amyloid-β (Aβ)], causes dominantly inherited Alzheimer's disease. Here, we report the high-resolution cryo-EM structures of Aβ filaments from the frontal cortex of a previously described case (AβPParc1) with the Arctic mutation. Most filaments consist of two pairs of non-identical protofilaments that comprise residues V12-V40 (human Arctic fold A) and E11-G37 (human Arctic fold B). They have a substructure (residues F20-G37) in common with the folds of type I and type II Aβ42. When compared to the structures of wild-type Aβ42 filaments, there are subtle conformational changes in the human Arctic folds, because of the lack of a side chain at G22, which may strengthen hydrogen bonding between mutant Aβ molecules and promote filament formation. A minority of Aβ42 filaments of type II was also present, as were tau paired helical filaments. In addition, we report the cryo-EM structures of Aβ filaments with the Arctic mutation from mouse knock-in line App. Most filaments are made of two identical mutant protofilaments that extend from D1 to G37 (App murine Arctic fold). In a minority of filaments, two dimeric folds pack against each other in an anti-parallel fashion. The App murine Arctic fold differs from the human Arctic folds, but shares some substructure. | |||||||||
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_16022.map.gz | 38.5 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-16022-v30.xml emd-16022.xml | 14.7 KB 14.7 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_16022_fsc.xml | 10.7 KB | 表示 | FSCデータファイル |
画像 | emd_16022.png | 151 KB | ||
Filedesc metadata | emd-16022.cif.gz | 4.9 KB | ||
その他 | emd_16022_half_map_1.map.gz emd_16022_half_map_2.map.gz | 37.4 MB 37.4 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-16022 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-16022 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_16022_validation.pdf.gz | 866.4 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_16022_full_validation.pdf.gz | 866 KB | 表示 | |
XML形式データ | emd_16022_validation.xml.gz | 18 KB | 表示 | |
CIF形式データ | emd_16022_validation.cif.gz | 23.7 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-16022 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-16022 | HTTPS FTP |
-関連構造データ
-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_16022.map.gz / 形式: CCP4 / 大きさ: 103 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: 0.653 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: #1
ファイル | emd_16022_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: #2
ファイル | emd_16022_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 : Amyloid-beta 42 dimeric filaments extracted from the human brain ...
全体 | 名称: Amyloid-beta 42 dimeric filaments extracted from the human brain with Arctic mutation (E22G) of Alzheimer's disease |
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要素 |
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-超分子 #1: Amyloid-beta 42 dimeric filaments extracted from the human brain ...
超分子 | 名称: Amyloid-beta 42 dimeric filaments extracted from the human brain with Arctic mutation (E22G) of Alzheimer's disease タイプ: tissue / 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 #1: Amyloid-beta precursor protein
分子 | 名称: Amyloid-beta precursor protein / タイプ: protein_or_peptide / ID: 1 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 4.520087 KDa |
配列 | 文字列: DAEFRHDSGY EVHHQKLVFF AEDVGSNKGA 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: 7.5 |
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凍結 | 凍結剤: ETHANE |
-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: GATAN K3 (6k x 4k) / 平均電子線量: 40.0 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): 2.2 µm / 最小 デフォーカス(公称値): 0.8 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |