+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-3851 | |||||||||
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タイトル | Near-atomic resolution fibril structure of complete amyloid-beta(1-42) by cryo-EM | |||||||||
マップデータ | The density map was sharpened by a B-factor of -50 Ang^2 and filtered to 3.5 Ang. This density map was used for model building and refinement. | |||||||||
試料 |
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キーワード | amyloid / fibril / aggregation / Alzheimer's disease / 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: 4.0 Å | |||||||||
データ登録者 | Gremer L / Schoelzel D | |||||||||
引用 | ジャーナル: Science / 年: 2017 タイトル: Fibril structure of amyloid-β(1-42) by cryo-electron microscopy. 著者: Lothar Gremer / Daniel Schölzel / Carla Schenk / Elke Reinartz / Jörg Labahn / Raimond B G Ravelli / Markus Tusche / Carmen Lopez-Iglesias / Wolfgang Hoyer / Henrike Heise / Dieter Willbold ...著者: Lothar Gremer / Daniel Schölzel / Carla Schenk / Elke Reinartz / Jörg Labahn / Raimond B G Ravelli / Markus Tusche / Carmen Lopez-Iglesias / Wolfgang Hoyer / Henrike Heise / Dieter Willbold / Gunnar F Schröder / 要旨: Amyloids are implicated in neurodegenerative diseases. Fibrillar aggregates of the amyloid-β protein (Aβ) are the main component of the senile plaques found in brains of Alzheimer's disease ...Amyloids are implicated in neurodegenerative diseases. Fibrillar aggregates of the amyloid-β protein (Aβ) are the main component of the senile plaques found in brains of Alzheimer's disease patients. We present the structure of an Aβ(1-42) fibril composed of two intertwined protofilaments determined by cryo-electron microscopy (cryo-EM) to 4.0-angstrom resolution, complemented by solid-state nuclear magnetic resonance experiments. The backbone of all 42 residues and nearly all side chains are well resolved in the EM density map, including the entire N terminus, which is part of the cross-β structure resulting in an overall "LS"-shaped topology of individual subunits. The dimer interface protects the hydrophobic C termini from the solvent. The characteristic staggering of the nonplanar subunits results in markedly different fibril ends, termed "groove" and "ridge," leading to different binding pathways on both fibril ends, which has implications for fibril growth. | |||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_3851.map.gz | 36.1 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-3851-v30.xml emd-3851.xml | 15.9 KB 15.9 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_3851_fsc.xml | 7.7 KB | 表示 | FSCデータファイル |
画像 | emd_3851.png | 147.8 KB | ||
Filedesc metadata | emd-3851.cif.gz | 5.5 KB | ||
その他 | emd_3851_half_map_1.map.gz emd_3851_half_map_2.map.gz | 13.5 MB 13.5 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-3851 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-3851 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_3851_validation.pdf.gz | 385 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_3851_full_validation.pdf.gz | 384.1 KB | 表示 | |
XML形式データ | emd_3851_validation.xml.gz | 13.4 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-3851 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-3851 | 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_3851.map.gz / 形式: CCP4 / 大きさ: 38.4 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | The density map was sharpened by a B-factor of -50 Ang^2 and filtered to 3.5 Ang. This density map was used for model building and refinement. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.935 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-ハーフマップ: even half map.
ファイル | emd_3851_half_map_1.map | ||||||||||||
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注釈 | even half map. | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: odd half map.
ファイル | emd_3851_half_map_2.map | ||||||||||||
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注釈 | odd half map. | ||||||||||||
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 : Beta-amyloid protein 42 fibrils
全体 | 名称: Beta-amyloid protein 42 fibrils |
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要素 |
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-超分子 #1: Beta-amyloid protein 42 fibrils
超分子 | 名称: Beta-amyloid protein 42 fibrils / 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 #1: Amyloid beta A4 protein
分子 | 名称: Amyloid beta A4 protein / タイプ: protein_or_peptide / ID: 1 / コピー数: 9 / 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 |
組換発現 | 生物種: Escherichia coli (大腸菌) |
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: 2 構成要素:
詳細: in water | ||||||
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グリッド | モデル: UltrAuFoil R 1.2/1.3 Quantifoil / 材質: GOLD / メッシュ: 300 / 前処理 - タイプ: GLOW DISCHARGE | ||||||
凍結 | 凍結剤: ETHANE / 装置: FEI VITROBOT MARK IV 詳細: 2.5 microL sample was applied to the grid, blotted for 2.5 s before plunging.. |
-電子顕微鏡法
顕微鏡 | FEI TECNAI 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: INTEGRATING / 撮影したグリッド数: 1 / 実像数: 2026 / 平均露光時間: 2.0 sec. / 平均電子線量: 24.0 e/Å2 |
電子線 | 加速電圧: 200 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 / Cs: 2.7 mm / 倍率(公称値): 110000 |
実験機器 | モデル: Talos Arctica / 画像提供: FEI Company |
-画像解析
-原子モデル構築 1
精密化 | 空間: REAL / プロトコル: AB INITIO MODEL 当てはまり具合の基準: Cross-correlation coefficient |
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得られたモデル | PDB-5oqv: |