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基本情報
登録情報 | データベース: EMDB / ID: EMD-20082 | |||||||||||||||
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タイトル | Amyloid-Beta (20-34) wild type | |||||||||||||||
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![]() | protofilament / 2 sub 1 screw symmetry / PROTEIN FIBRIL | |||||||||||||||
機能・相同性 | ![]() 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 | ![]() | |||||||||||||||
手法 | 電子線結晶学 / クライオ電子顕微鏡法 | |||||||||||||||
![]() | Sawaya MR / Warmack RA | |||||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structure of amyloid-β (20-34) with Alzheimer's-associated isomerization at Asp23 reveals a distinct protofilament interface. 著者: Rebeccah A Warmack / David R Boyer / Chih-Te Zee / Logan S Richards / Michael R Sawaya / Duilio Cascio / Tamir Gonen / David S Eisenberg / Steven G Clarke / ![]() 要旨: Amyloid-β (Aβ) harbors numerous posttranslational modifications (PTMs) that may affect Alzheimer's disease (AD) pathogenesis. Here we present the 1.1 Å resolution MicroED structure of an Aβ 20- ...Amyloid-β (Aβ) harbors numerous posttranslational modifications (PTMs) that may affect Alzheimer's disease (AD) pathogenesis. Here we present the 1.1 Å resolution MicroED structure of an Aβ 20-34 fibril with and without the disease-associated PTM, L-isoaspartate, at position 23 (L-isoAsp23). Both wild-type and L-isoAsp23 protofilaments adopt β-helix-like folds with tightly packed cores, resembling the cores of full-length fibrillar Aβ structures, and both self-associate through two distinct interfaces. One of these is a unique Aβ interface strengthened by the isoaspartyl modification. Powder diffraction patterns suggest a similar structure may be adopted by protofilaments of an analogous segment containing the heritable Iowa mutation, Asp23Asn. Consistent with its early onset phenotype in patients, Asp23Asn accelerates aggregation of Aβ 20-34, as does the L-isoAsp23 modification. These structures suggest that the enhanced amyloidogenicity of the modified Aβ segments may also reduce the concentration required to achieve nucleation and therefore help spur the pathogenesis of AD. | |||||||||||||||
履歴 |
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構造の表示
ムービー |
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構造ビューア | EMマップ: ![]() ![]() ![]() |
添付画像 |
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-EMDBアーカイブ
マップデータ | ![]() | 323.2 KB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 14.2 KB 14.2 KB | 表示 表示 | ![]() |
画像 | ![]() | 331.7 KB | ||
Filedesc metadata | ![]() | 5.5 KB | ||
Filedesc structureFactors | ![]() | 71.3 KB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 346.5 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 346 KB | 表示 | |
XML形式データ | ![]() | 4.3 KB | 表示 | |
CIF形式データ | ![]() | 4.7 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 6oizMC ![]() 0405C ![]() 6nb9C 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 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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ボクセルのサイズ | X: 0.296 Å / Y: 0.29875 Å / Z: 0.3033 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 4 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
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試料の構成要素
-全体 : crystal of amyloid-beta residues 20-34 wild type
全体 | 名称: crystal of amyloid-beta residues 20-34 wild type |
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要素 |
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-超分子 #1: crystal of amyloid-beta residues 20-34 wild type
超分子 | 名称: crystal of amyloid-beta residues 20-34 wild type / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1 |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 6.21 kDa/nm |
-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: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 1.491666 KDa |
配列 | 文字列: FAEDVGSNKG AIIGL UniProtKB: Amyloid-beta A4 protein |
-分子 #2: water
分子 | 名称: water / タイプ: ligand / ID: 2 / コピー数: 7 / 式: HOH |
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分子量 | 理論値: 18.015 Da |
Chemical component information | ![]() ChemComp-HOH: |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 電子線結晶学 |
試料の集合状態 | 3D array |
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試料調製
濃度 | 5.0 mg/mL | |||||||||||||||
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緩衝液 | pH: 7.5 構成要素:
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グリッド | モデル: Quantifoil, UltrAuFoil, R1.2/1.3 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY ARRAY / 支持フィルム - Film thickness: 30 / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 30 sec. / 詳細: 30 seconds on each side | |||||||||||||||
凍結 | 凍結剤: ETHANE / チャンバー内温度: 100 K / 装置: FEI VITROBOT MARK IV | |||||||||||||||
詳細 | This sample is a crystal. | |||||||||||||||
結晶化 | 装置: Varioscan plate reader / 雰囲気: air / 温度: 310.0 K / 時間: 30.0 HOUR / 詳細: shaken at 1200 rpm |
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電子顕微鏡法
顕微鏡 | FEI TALOS ARCTICA |
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温度 | 最低: 100.0 K / 最高: 100.0 K |
撮影 | フィルム・検出器のモデル: FEI CETA (4k x 4k) / デジタル化 - サイズ - 横: 2048 pixel / デジタル化 - サイズ - 縦: 2048 pixel / 撮影したグリッド数: 2 / 回折像の数: 404 / 平均露光時間: 3.0 sec. / 平均電子線量: 0.01 e/Å2 |
電子線 | 加速電圧: 200 kV / 電子線源: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: DIFFRACTION / カメラ長: 1050 mm |
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: Talos Arctica / 画像提供: FEI Company |
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画像解析
最終 再構成 | 解像度の算出法: DIFFRACTION PATTERN/LAYERLINES |
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Crystallography statistics | Number intensities measured: 23638 / Number structure factors: 3546 / Fourier space coverage: 85.2 / R sym: 0.189 / R merge: 0.189 / Overall phase error: 22.7 / Overall phase residual: 0.1 / Phase error rejection criteria: 0.1 / High resolution: 1.1 Å / 殻 - Shell ID: 1 / 殻 - High resolution: 1.0 Å / 殻 - Low resolution: 1.05 Å / 殻 - Number structure factors: 315 / 殻 - Phase residual: 0.1 / 殻 - Fourier space coverage: 41.2 / 殻 - Multiplicity: 3.09 |
-原子モデル構築 1
精密化 | 空間: RECIPROCAL / プロトコル: OTHER / 当てはまり具合の基準: maximum liklihood |
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得られたモデル | ![]() PDB-6oiz: |