+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-21501 | |||||||||
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タイトル | Amyloid-beta(1-40) fibril derived from Alzheimer's disease cortical tissue | |||||||||
マップデータ | CryoEM density map from RELION-based analysis | |||||||||
試料 |
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キーワード | amyloid-beta / Alzheimer's disease / 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: 2.77 Å | |||||||||
データ登録者 | Ghosh U / Thurber KR | |||||||||
引用 | ジャーナル: Proc Natl Acad Sci U S A / 年: 2021 タイトル: Molecular structure of a prevalent amyloid-β fibril polymorph from Alzheimer's disease brain tissue. 著者: Ujjayini Ghosh / Kent R Thurber / Wai-Ming Yau / Robert Tycko / 要旨: Amyloid-β (Aβ) fibrils exhibit self-propagating, molecular-level polymorphisms that may contribute to variations in clinical and pathological characteristics of Alzheimer's disease (AD). We report ...Amyloid-β (Aβ) fibrils exhibit self-propagating, molecular-level polymorphisms that may contribute to variations in clinical and pathological characteristics of Alzheimer's disease (AD). We report the molecular structure of a specific fibril polymorph, formed by 40-residue Aβ peptides (Aβ40), that is derived from cortical tissue of an AD patient by seeded fibril growth. The structure is determined from cryogenic electron microscopy (cryoEM) images, supplemented by mass-per-length (MPL) measurements and solid-state NMR (ssNMR) data. Previous ssNMR studies with multiple AD patients had identified this polymorph as the most prevalent brain-derived Aβ40 fibril polymorph from typical AD patients. The structure, which has 2.8-Å resolution according to standard criteria, differs qualitatively from all previously described Aβ fibril structures, both in its molecular conformations and its organization of cross-β subunits. Unique features include twofold screw symmetry about the fibril growth axis, despite an MPL value that indicates three Aβ40 molecules per 4.8-Å β-sheet spacing, a four-layered architecture, and fully extended conformations for molecules in the central two cross-β layers. The cryoEM density, ssNMR data, and MPL data are consistent with β-hairpin conformations for molecules in the outer cross-β layers. Knowledge of this brain-derived fibril structure may contribute to the development of structure-specific amyloid imaging agents and aggregation inhibitors with greater diagnostic and therapeutic utility. | |||||||||
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_21501.map.gz | 224.1 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-21501-v30.xml emd-21501.xml | 14.3 KB 14.3 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_21501_fsc.xml | 14.1 KB | 表示 | FSCデータファイル |
画像 | emd_21501.png | 120.4 KB | ||
マスクデータ | emd_21501_msk_1.map | 244.1 MB | マスクマップ | |
Filedesc metadata | emd-21501.cif.gz | 6.1 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-21501 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-21501 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_21501_validation.pdf.gz | 529.6 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_21501_full_validation.pdf.gz | 529.2 KB | 表示 | |
XML形式データ | emd_21501_validation.xml.gz | 13.9 KB | 表示 | |
CIF形式データ | emd_21501_validation.cif.gz | 18.7 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-21501 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-21501 | 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_21501.map.gz / 形式: CCP4 / 大きさ: 244.1 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | CryoEM density map from RELION-based analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: 1.08 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
-マスク #1
ファイル | emd_21501_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 |
-試料の構成要素
-全体 : amyloid-beta(1-40) fibrils derived from human AD brain
全体 | 名称: amyloid-beta(1-40) fibrils derived from human AD brain |
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要素 |
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-超分子 #1: amyloid-beta(1-40) fibrils derived from human AD brain
超分子 | 名称: amyloid-beta(1-40) fibrils derived from human AD brain タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all 詳細: Fibrils produced by seeded growth using amyloid-beta in brain extract as the source of seeds. CryoEM and solid state NMR measurements were performed on second-generation seeded fibrils. |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 29 kDa/nm |
-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
濃度 | 0.45 mg/mL |
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緩衝液 | pH: 7.4 / 構成要素 - 濃度: 10.0 mM / 構成要素 - 式: Na2HPO4/NaH2PO4 / 構成要素 - 名称: Phosphate buffer 詳細: 10 mM phosphate buffer with 0.01% NaN3 to avoid microbial contamination. Buffers were filtered to avoid contamination. |
グリッド | モデル: Quantifoil R1.2/1.3 / 材質: GOLD / メッシュ: 300 / 支持フィルム - トポロジー: HOLEY / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 60 sec. / 前処理 - 雰囲気: OTHER / 前処理 - 気圧: 0.036000000000000004 kPa / 詳細: The grids were checked in microscope prior to use. |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 90 % / チャンバー内温度: 293 K / 装置: LEICA PLUNGER 詳細: The grids were preblotted for 10 seconds and blotted for 6 seconds before plunging.. |
詳細 | Protein exists in solution as amyloid fibrils of varying lengths. |
-電子顕微鏡法
顕微鏡 | TFS KRIOS |
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アライメント法 | Coma free - Residual tilt: 6.0 mrad |
特殊光学系 | エネルギーフィルター - 名称: GIF Quantum LS / エネルギーフィルター - スリット幅: 20 eV |
詳細 | Preliminary grid screening was done manually in FEI T12. |
撮影 | フィルム・検出器のモデル: GATAN K2 QUANTUM (4k x 4k) 検出モード: SUPER-RESOLUTION / デジタル化 - 画像ごとのフレーム数: 1-50 / 撮影したグリッド数: 1 / 実像数: 1337 / 平均露光時間: 10.0 sec. / 平均電子線量: 73.5 e/Å2 |
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: 100.0 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): -3.0 µm / 最小 デフォーカス(公称値): -0.5 µm / 倍率(公称値): 130000 |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
+画像解析
-原子モデル構築 1
詳細 | Xplor-NIH was used to combine EM density with phi/psi restraints from NMR chemical shifts (from Talos-N Version 4.21 Rev 2016.343.11.31). |
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精密化 | 空間: REAL / プロトコル: AB INITIO MODEL |
得られたモデル | PDB-6w0o: |