+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-29037 | |||||||||
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タイトル | Amyloid-beta (1-40) fibrils derived from familial Dutch-type CAA patient (population B) | |||||||||
マップデータ | Final sharpened map. | |||||||||
試料 |
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キーワード | amyloid / vascular / fibril / human / PROTEIN FIBRIL | |||||||||
機能・相同性 | 機能・相同性情報 NMDA selective glutamate receptor signaling pathway / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / regulation of Wnt signaling pathway / axo-dendritic transport / synaptic assembly at neuromuscular junction / Formyl peptide receptors bind formyl peptides and many other ligands / signaling receptor activator activity ...NMDA selective glutamate receptor signaling pathway / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / regulation of Wnt signaling pathway / axo-dendritic transport / synaptic assembly at neuromuscular junction / Formyl peptide receptors bind formyl peptides and many other ligands / 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 / Lysosome Vesicle Biogenesis / ciliary rootlet / PTB domain binding / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / Golgi-associated vesicle / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / positive regulation of amyloid fibril formation / neuron remodeling / COPII-coated ER to Golgi transport vesicle / suckling behavior / nuclear envelope lumen / dendrite development / presynaptic active zone / modulation of excitatory postsynaptic potential / TRAF6 mediated NF-kB activation / The NLRP3 inflammasome / neuromuscular process controlling balance / Advanced glycosylation endproduct receptor signaling / transition metal ion binding / regulation of presynapse assembly / negative regulation of long-term synaptic potentiation / negative regulation of neuron differentiation / regulation of multicellular organism growth / intracellular copper ion homeostasis / ECM proteoglycans / trans-Golgi network membrane / smooth endoplasmic reticulum / positive regulation of T cell migration / spindle midzone / Purinergic signaling in leishmaniasis infection / clathrin-coated pit / protein serine/threonine kinase binding / regulation of peptidyl-tyrosine phosphorylation / positive regulation of chemokine production / forebrain development / Notch signaling pathway / neuron projection maintenance / Mitochondrial protein degradation / positive regulation of G2/M transition of mitotic cell cycle / positive regulation of protein metabolic process / cholesterol metabolic process / positive regulation of calcium-mediated signaling / ionotropic glutamate receptor signaling pathway / response to interleukin-1 / positive regulation of glycolytic process / axonogenesis / positive regulation of mitotic cell cycle / extracellular matrix organization / adult locomotory behavior / platelet alpha granule lumen / positive regulation of interleukin-1 beta production / learning / positive regulation of peptidyl-threonine phosphorylation / dendritic shaft / positive regulation of long-term synaptic potentiation / cognition / central nervous system development / endosome lumen / locomotory behavior / astrocyte activation / Post-translational protein phosphorylation / positive regulation of JNK cascade / microglial cell activation / regulation of long-term neuronal synaptic plasticity / synapse organization / serine-type endopeptidase inhibitor activity / TAK1-dependent IKK and NF-kappa-B activation / visual learning / neuromuscular junction / recycling endosome / positive regulation of interleukin-6 production / Golgi lumen / positive regulation of inflammatory response / neuron cellular homeostasis / positive regulation of non-canonical NF-kappaB signal transduction / endocytosis / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / cellular response to amyloid-beta / positive regulation of tumor necrosis factor production / G2/M transition of mitotic cell cycle / neuron projection development / cell-cell junction / Platelet degranulation / synaptic vesicle / apical part of cell 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: 3.09 Å | |||||||||
データ登録者 | Crooks EJ / Fu Z / Chowdury S / Smith SO | |||||||||
資金援助 | 米国, 2件
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引用 | ジャーナル: J Struct Biol / 年: 2024 タイトル: An electrostatic cluster guides Aβ40 fibril formation in sporadic and Dutch-type cerebral amyloid angiopathy. 著者: Ziao Fu / Elliot J Crooks / Brandon A Irizarry / Xiaoyue Zhu / Saikat Chowdhury / William E Van Nostrand / Steven O Smith / 要旨: Cerebral amyloid angiopathy (CAA) is associated with the accumulation of fibrillar Aβ peptides upon and within the cerebral vasculature, which leads to loss of vascular integrity and contributes to ...Cerebral amyloid angiopathy (CAA) is associated with the accumulation of fibrillar Aβ peptides upon and within the cerebral vasculature, which leads to loss of vascular integrity and contributes to disease progression in Alzheimer's disease (AD). We investigate the structure of human-derived Aβ40 fibrils obtained from patients diagnosed with sporadic or familial Dutch-type (E22Q) CAA. Using cryo-EM, two primary structures are identified containing elements that have not been observed in in vitro Aβ40 fibril structures. One population has an ordered N-terminal fold comprised of two β-strands stabilized by electrostatic interactions involving D1, E22, D23 and K28. This charged cluster is disrupted in the second population, which exhibits a disordered N-terminus and is favored in fibrils derived from the familial Dutch-type CAA patient. These results illustrate differences between human-derived CAA and AD fibrils, and how familial CAA mutations can guide fibril formation. | |||||||||
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_29037.map.gz | 50.7 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-29037-v30.xml emd-29037.xml | 17.5 KB 17.5 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_29037_fsc.xml | 8.7 KB | 表示 | FSCデータファイル |
画像 | emd_29037.png | 227.1 KB | ||
マスクデータ | emd_29037_msk_1.map | 56.8 MB | マスクマップ | |
Filedesc metadata | emd-29037.cif.gz | 5.5 KB | ||
その他 | emd_29037_half_map_1.map.gz emd_29037_half_map_2.map.gz | 43.7 MB 43.7 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-29037 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-29037 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_29037_validation.pdf.gz | 672.1 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_29037_full_validation.pdf.gz | 671.6 KB | 表示 | |
XML形式データ | emd_29037_validation.xml.gz | 14.5 KB | 表示 | |
CIF形式データ | emd_29037_validation.cif.gz | 20.7 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29037 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-29037 | 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_29037.map.gz / 形式: CCP4 / 大きさ: 56.8 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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注釈 | Final sharpened map. | ||||||||||||||||||||||||||||||||||||
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: 1.12 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_29037_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: Half-map 2.
ファイル | emd_29037_half_map_1.map | ||||||||||||
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注釈 | Half-map 2. | ||||||||||||
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 1.
ファイル | emd_29037_half_map_2.map | ||||||||||||
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注釈 | Half-map 1. | ||||||||||||
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 : Fibrillar assembly of human Amyloid-beta 1-40 from a familial Dut...
全体 | 名称: Fibrillar assembly of human Amyloid-beta 1-40 from a familial Dutch-type cerebral amyloid angiopathy patient |
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要素 |
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-超分子 #1: Fibrillar assembly of human Amyloid-beta 1-40 from a familial Dut...
超分子 | 名称: Fibrillar assembly of human Amyloid-beta 1-40 from a familial Dutch-type cerebral amyloid angiopathy patient 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 / 組織: Vasculature |
分子量 | 理論値: 4.3299 MDa |
-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: 6 / 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: 4.335852 KDa |
配列 | 文字列: DAEFRHDSGY EVHHQKLVFF AEDVGSNKGA IIGLMVGGVV 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 / チャンバー内湿度: 100 % / チャンバー内温度: 295 K / 装置: FEI VITROBOT MARK IV |
詳細 | Templated growth from human-derived vascular amyloid deposits |
-電子顕微鏡法
顕微鏡 | FEI TALOS ARCTICA |
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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: COUNTING / 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 - 画像ごとのフレーム数: 1-99 / 撮影したグリッド数: 1 / 実像数: 2140 / 平均露光時間: 86.11 sec. / 平均電子線量: 56.92 e/Å2 |
電子線 | 加速電圧: 200 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | C2レンズ絞り径: 70.0 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): 1.4000000000000001 µm 最小 デフォーカス(公称値): 0.6 µm / 倍率(公称値): 92000 |
試料ステージ | ホルダー冷却材: NITROGEN |
実験機器 | モデル: Talos Arctica / 画像提供: FEI Company |