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Yorodumi- EMDB-23871: Paired helical tau filament extracted from PrP-CAA Patient brain ... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-23871 | |||||||||
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Title | Paired helical tau filament extracted from PrP-CAA Patient brain tissue | tau filament | PHF Tau | |||||||||
Map data | 3 Angstrom resolution of PHF Tau from PrP-CAA | |||||||||
Sample |
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Function / homology | Function and homology information plus-end-directed organelle transport along microtubule / histone-dependent DNA binding / neurofibrillary tangle assembly / positive regulation of diacylglycerol kinase activity / axonal transport / 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 / histone-dependent DNA binding / neurofibrillary tangle assembly / positive regulation of diacylglycerol kinase activity / axonal transport / 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 / negative regulation of kinase activity / regulation of long-term synaptic depression / negative regulation of tubulin deacetylation / generation of neurons / rRNA metabolic process / internal protein amino acid acetylation / regulation of chromosome organization / regulation of mitochondrial fission / axonal transport of mitochondrion / intracellular distribution of mitochondria / axon development / central nervous system neuron development / regulation of microtubule polymerization / apolipoprotein binding / microtubule polymerization / lipoprotein particle binding / minor groove of adenine-thymine-rich DNA binding / dynactin binding / glial cell projection / negative regulation of mitochondrial membrane potential / protein polymerization / axolemma / negative regulation of mitochondrial fission / 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 / regulation of cellular response to heat / positive regulation of protein localization / cytoplasmic microtubule organization / stress granule assembly / supramolecular fiber organization / regulation of calcium-mediated signaling / axon cytoplasm / somatodendritic compartment / positive regulation of microtubule polymerization / synapse assembly / cellular response to brain-derived neurotrophic factor stimulus / 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 / microglial cell activation / synapse organization / Hsp90 protein binding / protein homooligomerization / PKR-mediated signaling / regulation of synaptic plasticity / : / memory / SH3 domain binding / microtubule cytoskeleton organization / cytoplasmic ribonucleoprotein granule / cellular response to reactive oxygen species / microtubule cytoskeleton / neuron projection development / cell-cell signaling / single-stranded DNA binding / protein-folding chaperone binding / actin binding / protein-macromolecule adaptor activity / cellular response to heat / double-stranded DNA binding / growth cone / cell body / microtubule binding / microtubule / sequence-specific DNA binding / amyloid fibril formation / 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 Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Human (human) | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||
Authors | Hoq M | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Acta Neuropathol / Year: 2021 Title: Structure of Tau filaments in Prion protein amyloidoses. Authors: Grace I Hallinan / Md Rejaul Hoq / Manali Ghosh / Frank S Vago / Anllely Fernandez / Holly J Garringer / Ruben Vidal / Wen Jiang / Bernardino Ghetti / Abstract: 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. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_23871.map.gz | 26.2 MB | EMDB map data format | |
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Header (meta data) | emd-23871-v30.xml emd-23871.xml | 10.2 KB 10.2 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_23871_fsc.xml | 13.7 KB | Display | FSC data file |
Images | emd_23871.png | 102.8 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-23871 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-23871 | HTTPS FTP |
-Validation report
Summary document | emd_23871_validation.pdf.gz | 365.8 KB | Display | EMDB validaton report |
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Full document | emd_23871_full_validation.pdf.gz | 365.4 KB | Display | |
Data in XML | emd_23871_validation.xml.gz | 12 KB | Display | |
Data in CIF | emd_23871_validation.cif.gz | 15.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23871 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23871 | HTTPS FTP |
-Related structure data
Related structure data | 7mkfMC 7mkgC 7mkhC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_23871.map.gz / Format: CCP4 / Size: 103 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | 3 Angstrom resolution of PHF Tau from PrP-CAA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.078 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : Paired helical filament (PHF) from PrP-CAA
Entire | Name: Paired helical filament (PHF) from PrP-CAA |
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Components |
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-Supramolecule #1: Paired helical filament (PHF) from PrP-CAA
Supramolecule | Name: Paired helical filament (PHF) from PrP-CAA / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: all Details: PHF tau in PrP-CAA, caused by the Q160X truncating mutation in PRNP |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Experimental: 55 kDa/nm |
-Macromolecule #1: PHF Tau from PrP-CAA Patient
Macromolecule | Name: PHF Tau from PrP-CAA Patient / type: other / ID: 1 / Classification: other |
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Source (natural) | Organism: Human (human) |
Sequence | String: QX |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | helical reconstruction |
Aggregation state | filament |
-Sample preparation
Concentration | 1 mg/mL |
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Buffer | pH: 7.4 |
Sugar embedding | Material: affinity tag |
Grid | Model: PELCO Ultrathin Carbon with Lacey Carbon / Material: COPPER / Mesh: 400 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Instrument: GATAN CRYOPLUNGE 3 |
Details | Filament extracted from frontal cortex of PrP-CAA patient brain |
-Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number real images: 2004 / Average electron dose: 1.067 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
-Atomic model buiding 1
Details | Each model was refined using Rosetta |
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Refinement | Space: RECIPROCAL / Overall B value: 24 / Target criteria: Fourier shell correlation |
Output model | PDB-7mkf: |