+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-13809 | |||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
タイトル | Type II beta-amyloid 42 Filaments from Human Brain | |||||||||||||||||||||
マップデータ | ||||||||||||||||||||||
試料 |
| |||||||||||||||||||||
機能・相同性 | 機能・相同性情報 regulation of epidermal growth factor-activated receptor activity / signaling receptor activator activity / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / Formyl peptide receptors bind formyl peptides and many other ligands / regulation of Wnt signaling pathway / axo-dendritic transport / synaptic assembly at neuromuscular junction ...regulation of epidermal growth factor-activated receptor activity / signaling receptor activator activity / cytosolic mRNA polyadenylation / collateral sprouting in absence of injury / microglia development / regulation of synapse structure or activity / Formyl peptide receptors bind formyl peptides and many other ligands / regulation of Wnt signaling pathway / axo-dendritic transport / synaptic assembly at neuromuscular junction / 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 / 繊毛 / 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 / protein serine/threonine kinase binding / Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models / : / nuclear envelope lumen / suckling behavior / presynaptic active zone / dendrite development / COPII-coated ER to Golgi transport vesicle / 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 / regulation of multicellular organism growth / intracellular copper ion homeostasis / negative regulation of long-term synaptic potentiation / negative regulation of neuron differentiation / ECM proteoglycans / 小胞体 / Mitochondrial protein degradation / positive regulation of T cell migration / spindle midzone / Purinergic signaling in leishmaniasis infection / positive regulation of calcium-mediated signaling / クラスリン / regulation of peptidyl-tyrosine phosphorylation / positive regulation of chemokine production / forebrain development / Notchシグナリング / positive regulation of G2/M transition of mitotic cell cycle / neuron projection maintenance / positive regulation of protein metabolic process / ionotropic glutamate receptor signaling pathway / positive regulation of glycolytic process / cholesterol metabolic process / response to interleukin-1 / positive regulation of mitotic cell cycle / extracellular matrix organization / 軸索誘導 / adult locomotory behavior / trans-Golgi network membrane / platelet alpha granule lumen / locomotory behavior / positive regulation of peptidyl-threonine phosphorylation / dendritic shaft / 学習 / positive regulation of interleukin-1 beta production / central nervous system development / positive regulation of long-term synaptic potentiation / endosome lumen / astrocyte activation / Post-translational protein phosphorylation / positive regulation of JNK cascade / synapse organization / regulation of long-term neuronal synaptic plasticity / microglial cell activation / TAK1-dependent IKK and NF-kappa-B activation / visual learning / serine-type endopeptidase inhibitor activity / neuromuscular junction / recycling endosome / 認識 / positive regulation of inflammatory response / Golgi lumen / neuron cellular homeostasis / エンドサイトーシス / positive regulation of non-canonical NF-kappaB signal transduction / cellular response to amyloid-beta / positive regulation of interleukin-6 production / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / neuron projection development / G2/M transition of mitotic cell cycle / positive regulation of tumor necrosis factor production / cell-cell junction / シナプス小胞 類似検索 - 分子機能 | |||||||||||||||||||||
生物種 | Homo sapiens (ヒト) / Human (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: 2.8 Å | |||||||||||||||||||||
データ登録者 | Yang Y / Arseni D / Zhang W / Huang M / Lovestam SKA / Schweighauser M / Kotecha A / Murzin AG / Peak-Chew SY / Macdonald J ...Yang Y / Arseni D / Zhang W / Huang M / Lovestam SKA / Schweighauser M / Kotecha A / Murzin AG / Peak-Chew SY / Macdonald J / Lavenir I / Garringer HJ / Gelpi E / Newell KL / Kovacs GG / Vidal R / Ghetti B / Falcon B / Scheres SHW / Goedert M | |||||||||||||||||||||
資金援助 | 米国, 6件
| |||||||||||||||||||||
引用 | ジャーナル: Science / 年: 2022 タイトル: Cryo-EM structures of amyloid-β 42 filaments from human brains. 著者: Yang Yang / Diana Arseni / Wenjuan Zhang / Melissa Huang / Sofia Lövestam / Manuel Schweighauser / Abhay Kotecha / Alexey G Murzin / Sew Y Peak-Chew / Jennifer Macdonald / Isabelle Lavenir / ...著者: Yang Yang / Diana Arseni / Wenjuan Zhang / Melissa Huang / Sofia Lövestam / Manuel Schweighauser / Abhay Kotecha / Alexey G Murzin / Sew Y Peak-Chew / Jennifer Macdonald / Isabelle Lavenir / Holly J Garringer / Ellen Gelpi / Kathy L Newell / Gabor G Kovacs / Ruben Vidal / Bernardino Ghetti / Benjamin Ryskeldi-Falcon / Sjors H W Scheres / Michel Goedert / 要旨: Filament assembly of amyloid-β peptides ending at residue 42 (Aβ42) is a central event in Alzheimer’s disease. Here, we report the cryo–electron microscopy (cryo-EM) structures of Aβ42 ...Filament assembly of amyloid-β peptides ending at residue 42 (Aβ42) is a central event in Alzheimer’s disease. Here, we report the cryo–electron microscopy (cryo-EM) structures of Aβ42 filaments from human brains. Two structurally related S-shaped protofilament folds give rise to two types of filaments. Type I filaments were found mostly in the brains of individuals with sporadic Alzheimer’s disease, and type II filaments were found in individuals with familial Alzheimer’s disease and other conditions. The structures of Aβ42 filaments from the brain differ from those of filaments assembled in vitro. By contrast, in knock-in mice, Aβ42 deposits were made of type II filaments. Knowledge of Aβ42 filament structures from human brains may lead to the development of inhibitors of assembly and improved imaging agents. | |||||||||||||||||||||
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_13809.map.gz | 22 MB | EMDBマップデータ形式 | |
---|---|---|---|---|
ヘッダ (付随情報) | emd-13809-v30.xml emd-13809.xml | 16.2 KB 16.2 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_13809_fsc.xml | 9.2 KB | 表示 | FSCデータファイル |
画像 | emd_13809.png | 43.4 KB | ||
その他 | emd_13809_half_map_1.map.gz emd_13809_half_map_2.map.gz | 21.1 MB 21.1 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-13809 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-13809 | HTTPS FTP |
-関連構造データ
関連構造データ | 7q4mMC 7q4bC 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 | |
電子顕微鏡画像生データ | EMPIAR-10917 (タイトル: Single particle cryo-EM dataset of sarkosyl-insoluble fraction from the frontal cortex of an individual with pathological aging of amyloid-β 42 filaments Data size: 203.1 Data #1: Unaligned multi-frame movies [micrographs - multiframe]) |
-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_13809.map.gz / 形式: CCP4 / 大きさ: 64 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
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: 0.73 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
|
-添付データ
-ハーフマップ: #2
ファイル | emd_13809_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_13809_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-試料の構成要素
-全体 : beta-amyloid 42 filaments extracted from the human brain with Alz...
全体 | 名称: beta-amyloid 42 filaments extracted from the human brain with Alzheimer's disease |
---|---|
要素 |
|
-超分子 #1: beta-amyloid 42 filaments extracted from the human brain with Alz...
超分子 | 名称: beta-amyloid 42 filaments extracted from the human brain with Alzheimer's disease タイプ: tissue / 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 precursor protein
分子 | 名称: Amyloid-beta precursor protein / タイプ: protein_or_peptide / ID: 1 / コピー数: 10 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: Human (ヒト) |
分子量 | 理論値: 4.520087 KDa |
配列 | 文字列: DAEFRHDSGY EVHHQKLVFF AEDVGSNKGA IIGLMVGGVV IA |
-分子 #2: UNKNOWN ATOM OR ION
分子 | 名称: UNKNOWN ATOM OR ION / タイプ: ligand / ID: 2 / コピー数: 10 / 式: UNX |
---|
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
---|---|
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: 7.5 |
---|---|
凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
---|---|
電子線 | 加速電圧: 300 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 FIELDBright-field microscopy |
撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均電子線量: 40.0 e/Å2 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |