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基本情報
登録情報 | データベース: PDB / ID: 5oqv | ||||||
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タイトル | Near-atomic resolution fibril structure of complete amyloid-beta(1-42) by cryo-EM | ||||||
![]() | Amyloid beta A4 protein | ||||||
![]() | PROTEIN FIBRIL / amyloid / fibril / aggregation / Alzheimer's disease | ||||||
機能・相同性 | ![]() amyloid-beta complex / negative regulation of presynapse assembly / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of Wnt signaling pathway / synaptic assembly at neuromuscular junction / Formyl peptide receptors bind formyl peptides and many other ligands / regulation of synapse structure or activity / axo-dendritic transport ...amyloid-beta complex / negative regulation of presynapse assembly / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of Wnt signaling pathway / synaptic assembly at neuromuscular junction / Formyl peptide receptors bind formyl peptides and many other ligands / regulation of synapse structure or activity / axo-dendritic transport / axon midline choice point recognition / smooth endoplasmic reticulum calcium ion homeostasis / astrocyte activation involved in immune response / NMDA selective glutamate receptor signaling pathway / mating behavior / regulation of spontaneous synaptic transmission / ciliary rootlet / Golgi-associated vesicle / PTB domain binding / Lysosome Vesicle Biogenesis / Insertion of tail-anchored proteins into the endoplasmic reticulum membrane / positive regulation of amyloid fibril formation / neuron remodeling / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / nuclear envelope lumen / COPII-coated ER to Golgi transport vesicle / suckling behavior / signaling receptor activator activity / dendrite development / modulation of excitatory postsynaptic potential / TRAF6 mediated NF-kB activation / presynaptic active zone / positive regulation of protein metabolic process / Advanced glycosylation endproduct receptor signaling / The NLRP3 inflammasome / neuromuscular process controlling balance / negative regulation of long-term synaptic potentiation / regulation of multicellular organism growth / transition metal ion binding / intracellular copper ion homeostasis / regulation of presynapse assembly / negative regulation of neuron differentiation / ECM proteoglycans / spindle midzone / positive regulation of T cell migration / smooth endoplasmic reticulum / Purinergic signaling in leishmaniasis infection / forebrain development / positive regulation of chemokine production / clathrin-coated pit / Notch signaling pathway / positive regulation of G2/M transition of mitotic cell cycle / protein serine/threonine kinase binding / extracellular matrix organization / neuron projection maintenance / Mitochondrial protein degradation / ionotropic glutamate receptor signaling pathway / response to interleukin-1 / positive regulation of mitotic cell cycle / cholesterol metabolic process / axonogenesis / positive regulation of calcium-mediated signaling / platelet alpha granule lumen / adult locomotory behavior / positive regulation of glycolytic process / dendritic shaft / central nervous system development / learning / positive regulation of interleukin-1 beta production / trans-Golgi network membrane / positive regulation of long-term synaptic potentiation / endosome lumen / locomotory behavior / astrocyte activation / Post-translational protein phosphorylation / positive regulation of JNK cascade / microglial cell activation / serine-type endopeptidase inhibitor activity / regulation of long-term neuronal synaptic plasticity / synapse organization / TAK1-dependent IKK and NF-kappa-B activation / positive regulation of non-canonical NF-kappaB signal transduction / visual learning / neuromuscular junction / recycling endosome / positive regulation of interleukin-6 production / Golgi lumen / cognition / neuron cellular homeostasis / positive regulation of inflammatory response / endocytosis / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / cellular response to amyloid-beta / neuron projection development / G2/M transition of mitotic cell cycle / positive regulation of tumor necrosis factor production / apical part of cell / synaptic vesicle / cell-cell junction / Platelet degranulation 類似検索 - 分子機能 | ||||||
生物種 | ![]() | ||||||
手法 | 電子顕微鏡法 / らせん対称体再構成法 / クライオ電子顕微鏡法 / 解像度: 4 Å | ||||||
![]() | Gremer, L. / Schoelzel, D. / Schenk, C. / Reinartz, E. / Labahn, J. / Ravelli, R. / Tusche, M. / Lopez-Iglesias, C. / Hoyer, W. / Heise, H. ...Gremer, L. / Schoelzel, D. / Schenk, C. / Reinartz, E. / Labahn, J. / Ravelli, R. / Tusche, M. / Lopez-Iglesias, C. / Hoyer, W. / Heise, H. / Willbold, D. / Schroeder, G.F. | ||||||
![]() | ![]() 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. | ||||||
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構造の表示
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構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 124.3 KB | 表示 | ![]() |
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-検証レポート
文書・要旨 | ![]() | 1.1 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.1 MB | 表示 | |
XML形式データ | ![]() | 25.1 KB | 表示 | |
CIF形式データ | ![]() | 36.2 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 | ![]() 3851MC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 ( |
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集合体
登録構造単位 | ![]()
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要素
#1: タンパク質・ペプチド | 分子量: 4520.087 Da / 分子数: 9 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: FILAMENT / 3次元再構成法: らせん対称体再構成法 |
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試料調製
構成要素 | 名称: Beta-amyloid protein 42 fibrils / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT | ||||||||||||
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分子量 | 実験値: NO | ||||||||||||
由来(天然) | 生物種: ![]() | ||||||||||||
由来(組換発現) | 生物種: ![]() ![]() | ||||||||||||
緩衝液 | pH: 2 / 詳細: in water | ||||||||||||
緩衝液成分 |
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試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||
試料支持 | グリッドの材料: GOLD / グリッドのサイズ: 300 divisions/in. / グリッドのタイプ: UltrAuFoil R 1.2/1.3 Quantifoil | ||||||||||||
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE 詳細: 2.5 microL sample was applied to the grid, blotted for 2.5 s before plunging. |
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電子顕微鏡撮影
実験機器 | ![]() モデル: Talos Arctica / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TECNAI ARCTICA |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD / 倍率(公称値): 110000 X / Cs: 2.7 mm |
撮影 | 平均露光時間: 2 sec. / 電子線照射量: 24 e/Å2 / 検出モード: INTEGRATING フィルム・検出器のモデル: FEI FALCON III (4k x 4k) 撮影したグリッド数: 1 / 実像数: 2026 |
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解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||||||||||
らせん対称 | 回転角度/サブユニット: -179.275 ° / 軸方向距離/サブユニット: 2.335 Å / らせん対称軸の対称性: C1 | |||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 127765 詳細: For the even/odd test, the fibrils were split after the final reconstruction (no gold-standard). These two half sets were then refined further independently for another 12 iterations. クラス平均像の数: 1 / 対称性のタイプ: HELICAL | |||||||||||||||||||||||||||||||||||
原子モデル構築 | プロトコル: AB INITIO MODEL / 空間: REAL / Target criteria: Cross-correlation coefficient |