+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-8720 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
タイトル | VGSNKGAIIGL from Amyloid Beta determined by MicroED | |||||||||
マップデータ | VGSNKGAIIGL from Amyloid Beta | |||||||||
試料 |
| |||||||||
キーワード | Amyloid / steric zipper / 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 | 電子線結晶学 / クライオ電子顕微鏡法 | |||||||||
データ登録者 | Rodriguez JA / Sawaya MR / Cascio D / Eisenberg DS / Griner SL / Gonen T | |||||||||
資金援助 | 米国, 1件
| |||||||||
引用 | ジャーナル: J Biol Chem / 年: 2018 タイトル: Common fibrillar spines of amyloid-β and human islet amyloid polypeptide revealed by microelectron diffraction and structure-based inhibitors. 著者: Pascal Krotee / Sarah L Griner / Michael R Sawaya / Duilio Cascio / Jose A Rodriguez / Dan Shi / Stephan Philipp / Kevin Murray / Lorena Saelices / Ji Lee / Paul Seidler / Charles G Glabe / ...著者: Pascal Krotee / Sarah L Griner / Michael R Sawaya / Duilio Cascio / Jose A Rodriguez / Dan Shi / Stephan Philipp / Kevin Murray / Lorena Saelices / Ji Lee / Paul Seidler / Charles G Glabe / Lin Jiang / Tamir Gonen / David S Eisenberg / 要旨: Amyloid-β (Aβ) and human islet amyloid polypeptide (hIAPP) aggregate to form amyloid fibrils that deposit in tissues and are associated with Alzheimer's disease (AD) and type II diabetes (T2D), ...Amyloid-β (Aβ) and human islet amyloid polypeptide (hIAPP) aggregate to form amyloid fibrils that deposit in tissues and are associated with Alzheimer's disease (AD) and type II diabetes (T2D), respectively. Individuals with T2D have an increased risk of developing AD, and conversely, AD patients have an increased risk of developing T2D. Evidence suggests that this link between AD and T2D might originate from a structural similarity between aggregates of Aβ and hIAPP. Using the cryoEM method microelectron diffraction, we determined the atomic structures of 11-residue segments from both Aβ and hIAPP, termed Aβ(24-34) WT and hIAPP(19-29) S20G, with 64% sequence similarity. We observed a high degree of structural similarity between their backbone atoms (0.96-Å root mean square deviation). Moreover, fibrils of these segments induced amyloid formation through self- and cross-seeding. Furthermore, inhibitors designed for one segment showed cross-efficacy for full-length Aβ and hIAPP and reduced cytotoxicity of both proteins, although by apparently blocking different cytotoxic mechanisms. The similarity of the atomic structures of Aβ(24-34) WT and hIAPP(19-29) S20G offers a molecular model for cross-seeding between Aβ and hIAPP. | |||||||||
履歴 |
|
-構造の表示
ムービー |
ムービービューア |
---|---|
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_8720.map.gz | 148.4 KB | EMDBマップデータ形式 | |
---|---|---|---|---|
ヘッダ (付随情報) | emd-8720-v30.xml emd-8720.xml | 13.2 KB 13.2 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_8720.png | 288 KB | ||
Filedesc metadata | emd-8720.cif.gz | 5.1 KB | ||
Filedesc structureFactors | emd_8720_sf.cif.gz | 27.9 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-8720 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-8720 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_8720_validation.pdf.gz | 361.4 KB | 表示 | EMDB検証レポート |
---|---|---|---|---|
文書・詳細版 | emd_8720_full_validation.pdf.gz | 361 KB | 表示 | |
XML形式データ | emd_8720_validation.xml.gz | 4.2 KB | 表示 | |
CIF形式データ | emd_8720_validation.cif.gz | 4.6 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-8720 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-8720 | HTTPS FTP |
-関連構造データ
関連構造データ | 5vosMC 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 (文献) |
---|---|
類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
---|---|
「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_8720.map.gz / 形式: CCP4 / 大きさ: 211.9 KB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | VGSNKGAIIGL from Amyloid Beta | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
投影像・断面図 | 画像のコントロール
画像は Spider により作成 これらの図は立方格子座標系で作成されたものです | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X: 0.4675 Å / Y: 0.3916 Å / Z: 0.4648 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
対称性 | 空間群: 4 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
|
-添付データ
-試料の構成要素
-全体 : Fibrils of Amyloid Beta segment 24-34
全体 | 名称: Fibrils of Amyloid Beta segment 24-34 |
---|---|
要素 |
|
-超分子 #1: Fibrils of Amyloid Beta segment 24-34
超分子 | 名称: Fibrils of Amyloid Beta segment 24-34 / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1 |
---|---|
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: 1 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 1.029213 KDa |
配列 | 文字列: VGSNKGAIIG L UniProtKB: Amyloid-beta A4 protein |
-分子 #2: water
分子 | 名称: water / タイプ: ligand / ID: 2 / コピー数: 1 / 式: HOH |
---|---|
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 |
---|---|
解析 | 電子線結晶学 |
試料の集合状態 | 3D array |
-試料調製
濃度 | 7.5 mg/mL | ||||||
---|---|---|---|---|---|---|---|
緩衝液 | pH: 4 / 構成要素:
| ||||||
グリッド | モデル: Quantifoil / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY / 前処理 - タイプ: GLOW DISCHARGE | ||||||
凍結 | 凍結剤: ETHANE / 装置: FEI VITROBOT MARK IV | ||||||
詳細 | nanocrystals | ||||||
結晶化 | 装置: microcentrifuge tube / 雰囲気: air / 温度: 310.0 K / 時間: 2.0 DAY / 詳細: shaking |
-電子顕微鏡法
顕微鏡 | FEI TECNAI F20 |
---|---|
撮影 | フィルム・検出器のモデル: TVIPS TEMCAM-F416 (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 / 回折像の数: 471 / 平均電子線量: 0.03 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: DIFFRACTION / カメラ長: 1840 mm |
試料ステージ | 試料ホルダーモデル: GATAN 626 SINGLE TILT LIQUID NITROGEN CRYO TRANSFER HOLDER ホルダー冷却材: NITROGEN |
実験機器 | モデル: Tecnai F20 / 画像提供: FEI Company |
-画像解析
最終 再構成 | 解像度の算出法: DIFFRACTION PATTERN/LAYERLINES |
---|---|
Molecular replacement | ソフトウェア - 名称: phaser |
Merging software list | ソフトウェア - 名称: XSCALE (ver. Jun 17, 2015) |
Crystallography statistics | Number intensities measured: 5843 / Number structure factors: 1129 / Fourier space coverage: 85.5 / R sym: 0.222 / R merge: 0.222 / Overall phase error: 0 / Overall phase residual: 0.01 / Phase error rejection criteria: 0 / High resolution: 1.42 Å / 殻 - Shell ID: 1 / 殻 - High resolution: 1.42 Å / 殻 - Low resolution: 1.49 Å / 殻 - Number structure factors: 84 / 殻 - Phase residual: 0.01 / 殻 - Fourier space coverage: 47.5 / 殻 - Multiplicity: 2.6 |
-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 likelihood |
---|---|
得られたモデル | PDB-5vos: |