- EMDB-23871: Paired helical tau filament extracted from PrP-CAA Patient brain ... -
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基本情報
登録情報
データベース: EMDB / ID: EMD-23871
タイトル
Paired helical tau filament extracted from PrP-CAA Patient brain tissue | tau filament | PHF Tau
マップデータ
3 Angstrom resolution of PHF Tau from PrP-CAA
試料
細胞器官・細胞要素: Paired helical filament (PHF) from PrP-CAA
Other: PHF Tau from PrP-CAA Patient
機能・相同性
機能・相同性情報
plus-end-directed organelle transport along microtubule / axonal transport / histone-dependent DNA binding / neurofibrillary tangle assembly / positive regulation of diacylglycerol kinase activity / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / positive regulation of protein localization to synapse / microtubule lateral binding / tubulin complex ...plus-end-directed organelle transport along microtubule / axonal transport / histone-dependent DNA binding / neurofibrillary tangle assembly / positive regulation of diacylglycerol kinase activity / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / positive regulation of protein localization to synapse / microtubule lateral binding / tubulin complex / phosphatidylinositol bisphosphate binding / main axon / regulation of long-term synaptic depression / negative regulation of kinase activity / negative regulation of tubulin deacetylation / generation of neurons / regulation of chromosome organization / positive regulation of protein localization / rRNA metabolic process / internal protein amino acid acetylation / regulation of mitochondrial fission / intracellular distribution of mitochondria / axonal transport of mitochondrion / axon development / central nervous system neuron development / regulation of microtubule polymerization / microtubule polymerization / minor groove of adenine-thymine-rich DNA binding / lipoprotein particle binding / dynactin binding / apolipoprotein binding / glial cell projection / negative regulation of mitochondrial membrane potential / protein polymerization / negative regulation of mitochondrial fission / axolemma / Caspase-mediated cleavage of cytoskeletal proteins / regulation of microtubule polymerization or depolymerization / positive regulation of axon extension / regulation of microtubule cytoskeleton organization / Activation of AMPK downstream of NMDARs / supramolecular fiber organization / regulation of cellular response to heat / stress granule assembly / cytoplasmic microtubule organization / regulation of calcium-mediated signaling / axon cytoplasm / positive regulation of microtubule polymerization / somatodendritic compartment / cellular response to brain-derived neurotrophic factor stimulus / synapse assembly / phosphatidylinositol binding / nuclear periphery / cellular response to nerve growth factor stimulus / positive regulation of superoxide anion generation / protein phosphatase 2A binding / regulation of autophagy / astrocyte activation / response to lead ion / synapse organization / microglial cell activation / Hsp90 protein binding / regulation of synaptic plasticity / PKR-mediated signaling / protein homooligomerization / memory / cytoplasmic ribonucleoprotein granule / cellular response to reactive oxygen species / SH3 domain binding / microtubule cytoskeleton organization / activation of cysteine-type endopeptidase activity involved in apoptotic process / neuron projection development / microtubule cytoskeleton / cell-cell signaling / protein-macromolecule adaptor activity / actin binding / single-stranded DNA binding / cellular response to heat / protein-folding chaperone binding / cell body / growth cone / microtubule binding / double-stranded DNA binding / microtubule / amyloid fibril formation / sequence-specific DNA binding / dendritic spine / learning or memory / nuclear speck / neuron projection / membrane raft / axon / negative regulation of gene expression / neuronal cell body / DNA damage response / dendrite / protein kinase binding / enzyme binding / mitochondrion / DNA binding 類似検索 - 分子機能
: / Microtubule associated protein, tubulin-binding repeat / Microtubule-associated protein Tau / Tau and MAP protein, tubulin-binding repeat / Tau and MAP proteins tubulin-binding repeat signature. / Tau and MAP proteins tubulin-binding repeat profile. 類似検索 - ドメイン・相同性
Microtubule-associated protein tau / Isoform Tau-F of Microtubule-associated protein tau 類似検索 - 構成要素
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
R01-AG071177
米国
引用
ジャーナル: Acta Neuropathol / 年: 2021 タイトル: Structure of Tau filaments in Prion protein amyloidoses. 著者: Grace I Hallinan / Md Rejaul Hoq / Manali Ghosh / Frank S Vago / Anllely Fernandez / Holly J Garringer / Ruben Vidal / Wen Jiang / Bernardino Ghetti / 要旨: In human neurodegenerative diseases associated with the intracellular aggregation of Tau protein, the ordered cores of Tau filaments adopt distinct folds. Here, we analyze Tau filaments isolated from ...In human neurodegenerative diseases associated with the intracellular aggregation of Tau protein, the ordered cores of Tau filaments adopt distinct folds. Here, we analyze Tau filaments isolated from the brain of individuals affected by Prion-Protein cerebral amyloid angiopathy (PrP-CAA) with a nonsense mutation in the PRNP gene that leads to early termination of translation of PrP (Q160Ter or Q160X), and Gerstmann-Sträussler-Scheinker (GSS) disease, with a missense mutation in the PRNP gene that leads to an amino acid substitution at residue 198 (F198S) of PrP. The clinical and neuropathologic phenotypes associated with these two mutations in PRNP are different; however, the neuropathologic analyses of these two genetic variants have consistently shown the presence of numerous neurofibrillary tangles (NFTs) made of filamentous Tau aggregates in neurons. We report that Tau filaments in PrP-CAA (Q160X) and GSS (F198S) are composed of 3-repeat and 4-repeat Tau isoforms, having a striking similarity to NFTs in Alzheimer disease (AD). In PrP-CAA (Q160X), Tau filaments are made of both paired helical filaments (PHFs) and straight filaments (SFs), while in GSS (F198S), only PHFs were found. Mass spectrometry analyses of Tau filaments extracted from PrP-CAA (Q160X) and GSS (F198S) brains show the presence of post-translational modifications that are comparable to those seen in Tau aggregates from AD. Cryo-EM analysis reveals that the atomic models of the Tau filaments obtained from PrP-CAA (Q160X) and GSS (F198S) are identical to those of the Tau filaments from AD, and are therefore distinct from those of Pick disease, chronic traumatic encephalopathy, and corticobasal degeneration. Our data support the hypothesis that in the presence of extracellular amyloid deposits and regardless of the primary amino acid sequence of the amyloid protein, similar molecular mechanisms are at play in the formation of identical Tau filaments.
ダウンロード / ファイル: emd_23871.map.gz / 形式: CCP4 / 大きさ: 103 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
注釈
3 Angstrom resolution of PHF Tau from PrP-CAA
ボクセルのサイズ
X=Y=Z: 1.078 Å
密度
表面レベル
登録者による: 0.0219 / ムービー #1: 0.0219
最小 - 最大
-0.025854126 - 0.055417214
平均 (標準偏差)
0.0010129404 (±0.0040244916)
対称性
空間群: 1
詳細
EMDB XML:
マップ形状
Axis order
X
Y
Z
Origin
0
0
0
サイズ
300
300
300
Spacing
300
300
300
セル
A=B=C: 323.4 Å α=β=γ: 90.0 °
CCP4マップ ヘッダ情報:
mode
Image stored as Reals
Å/pix. X/Y/Z
1.078
1.078
1.078
M x/y/z
300
300
300
origin x/y/z
0.000
0.000
0.000
length x/y/z
323.400
323.400
323.400
α/β/γ
90.000
90.000
90.000
MAP C/R/S
1
2
3
start NC/NR/NS
0
0
0
NC/NR/NS
300
300
300
D min/max/mean
-0.026
0.055
0.001
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添付データ
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試料の構成要素
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全体 : Paired helical filament (PHF) from PrP-CAA
全体
名称: Paired helical filament (PHF) from PrP-CAA
要素
細胞器官・細胞要素: Paired helical filament (PHF) from PrP-CAA
Other: PHF Tau from PrP-CAA Patient
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超分子 #1: Paired helical filament (PHF) from PrP-CAA
超分子
名称: Paired helical filament (PHF) from PrP-CAA / タイプ: organelle_or_cellular_component / ID: 1 / 親要素: 0 / 含まれる分子: all 詳細: PHF tau in PrP-CAA, caused by the Q160X truncating mutation in PRNP
由来(天然)
生物種: Homo sapiens (ヒト)
分子量
実験値: 55 kDa/nm
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分子 #1: PHF Tau from PrP-CAA Patient
分子
名称: PHF Tau from PrP-CAA Patient / タイプ: other / ID: 1 / 分類: other