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Yorodumi- EMDB-18269: P301S Tau Filaments from the Brains of Tg2541 Transgenic Mouse Line -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-18269 | |||||||||
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Title | P301S Tau Filaments from the Brains of Tg2541 Transgenic Mouse Line | |||||||||
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Sample |
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Keywords | P301S tau / Frontotemporal dementia and parkinsonism linked to chromosome 17 / Transgenic mice / Electron cryo-microscopy / PROTEIN FIBRIL | |||||||||
Function / homology | Function and homology information Caspase-mediated cleavage of cytoskeletal proteins / negative regulation of intracellular transport / positive regulation of long-term synaptic depression / regulation of microtubule-based movement / PKR-mediated signaling / axon extension / axo-dendritic transport / adult walking behavior / mitochondrion transport along microtubule / negative regulation of establishment of protein localization to mitochondrion ...Caspase-mediated cleavage of cytoskeletal proteins / negative regulation of intracellular transport / positive regulation of long-term synaptic depression / regulation of microtubule-based movement / PKR-mediated signaling / axon extension / axo-dendritic transport / adult walking behavior / mitochondrion transport along microtubule / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / positive regulation of protein localization to synapse / microtubule lateral binding / tubulin complex / main axon / negative regulation of tubulin deacetylation / intrinsic apoptotic signaling pathway in response to oxidative stress / positive regulation of protein localization / intracellular distribution of mitochondria / microtubule polymerization / axoneme / lipoprotein particle binding / glial cell projection / negative regulation of mitochondrial membrane potential / apolipoprotein binding / protein polymerization / negative regulation of mitochondrial fission / axolemma / intracellular transport / regulation of microtubule polymerization or depolymerization / positive regulation of axon extension / mRNA transport / supramolecular fiber organization / regulation of microtubule cytoskeleton organization / axonal growth cone / regulation of cellular response to heat / regulation of calcium-mediated signaling / positive regulation of microtubule polymerization / somatodendritic compartment / synapse assembly / heat shock protein binding / axonogenesis / nuclear periphery / response to nutrient / positive regulation of superoxide anion generation / protein phosphatase 2A binding / response to organic substance / regulation of autophagy / synapse organization / response to lead ion / neuron migration / Hsp90 protein binding / protein homooligomerization / cytoplasmic side of plasma membrane / cytoplasmic ribonucleoprotein granule / memory / microtubule cytoskeleton organization / positive regulation of neuron projection development / SH3 domain binding / neuron projection development / microtubule cytoskeleton / cell body / growth cone / protein-folding chaperone binding / microtubule binding / microtubule / amyloid fibril formation / postsynaptic density / learning or memory / neuron projection / nuclear speck / membrane raft / axon / negative regulation of gene expression / neuronal cell body / dendrite / DNA damage response / protein-containing complex binding / protein kinase binding / enzyme binding / DNA binding / extracellular region / identical protein binding / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | Mus musculus (house mouse) | |||||||||
Method | helical reconstruction / cryo EM / Resolution: 3.09 Å | |||||||||
Authors | Schweighauser M / Murzin AG / Macdonald J / Lavenir I / Crowther RA / Scheres SHW / Goedert M | |||||||||
Funding support | United Kingdom, 2 items
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Citation | Journal: Acta Neuropathol Commun / Year: 2023 Title: Cryo-EM structures of tau filaments from the brains of mice transgenic for human mutant P301S Tau. Authors: Manuel Schweighauser / Alexey G Murzin / Jennifer Macdonald / Isabelle Lavenir / R Anthony Crowther / Sjors H W Scheres / Michel Goedert / Abstract: Mice transgenic for human mutant P301S tau are widely used as models for human tauopathies. They develop neurodegeneration and abundant filamentous inclusions made of human mutant four-repeat tau. ...Mice transgenic for human mutant P301S tau are widely used as models for human tauopathies. They develop neurodegeneration and abundant filamentous inclusions made of human mutant four-repeat tau. Here we used electron cryo-microscopy (cryo-EM) to determine the structures of tau filaments from the brains of Tg2541 and PS19 mice. Both lines express human P301S tau (0N4R for Tg2541 and 1N4R for PS19) on mixed genetic backgrounds and downstream of different promoters (murine Thy1 for Tg2541 and murine Prnp for PS19). The structures of tau filaments from Tg2541 and PS19 mice differ from each other and those of wild-type tau filaments from human brains. The structures of tau filaments from the brains of humans with mutations P301L, P301S or P301T in MAPT are not known. Filaments from the brains of Tg2541 and PS19 mice share a substructure at the junction of repeats 2 and 3, which comprises residues I297-V312 of tau and includes the P301S mutation. The filament core from the brainstem of Tg2541 mice consists of residues K274-H329 of tau and two disconnected protein densities. Two non-proteinaceous densities are also in evidence. The filament core from the cerebral cortex of line PS19 extends from residues G271-P364 of tau. One strong non-proteinaceous density is also present. Unlike the tau filaments from human brains, the sequences following repeat 4 are missing from the cores of tau filaments from the brains of Tg2541 and PS19 mice. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_18269.map.gz | 13.4 MB | EMDB map data format | |
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Header (meta data) | emd-18269-v30.xml emd-18269.xml | 16.5 KB 16.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_18269_fsc.xml | 7.8 KB | Display | FSC data file |
Images | emd_18269.png | 30.1 KB | ||
Masks | emd_18269_msk_1.map | 40.6 MB | Mask map | |
Filedesc metadata | emd-18269.cif.gz | 5.1 KB | ||
Others | emd_18269_half_map_1.map.gz emd_18269_half_map_2.map.gz | 31.3 MB 31.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-18269 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-18269 | HTTPS FTP |
-Related structure data
Related structure data | 8q96MC 8q92C M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_18269.map.gz / Format: CCP4 / Size: 40.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.15 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_18269_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_18269_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_18269_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : P301S Tau Protein Filament (Tg2541)
Entire | Name: P301S Tau Protein Filament (Tg2541) |
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Components |
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-Supramolecule #1: P301S Tau Protein Filament (Tg2541)
Supramolecule | Name: P301S Tau Protein Filament (Tg2541) / type: tissue / ID: 1 / Parent: 0 / Macromolecule list: all Details: Human P301S tau filaments extracted from the brains of transgenic mouse line Tg2541 |
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Source (natural) | Organism: Mus musculus (house mouse) / Strain: Tg2541 / Organ: Brain / Tissue: Brainstem |
-Macromolecule #1: Isoform Tau-E of Microtubule-associated protein tau
Macromolecule | Name: Isoform Tau-E of Microtubule-associated protein tau / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) / Strain: Tg2541 / Organ: Brain / Tissue: Brainstem |
Molecular weight | Theoretical: 5.961934 KDa |
Sequence | String: KVQIINKKLD LSNVQSKCGS KDNIKHVSGG GSVQIVYKPV DLSKVTSKCG SLGNIH UniProtKB: Microtubule-associated protein tau |
-Macromolecule #2: Unknown protein
Macromolecule | Name: Unknown protein / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) / Strain: Tg2541 / Organ: Brain / Tissue: Brainstem |
Molecular weight | Theoretical: 1.039273 KDa |
Sequence | String: (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK) |
-Macromolecule #3: Unknown protein
Macromolecule | Name: Unknown protein / type: protein_or_peptide / ID: 3 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) / Strain: Tg2541 / Organ: Brain / Tissue: Brainstem |
Molecular weight | Theoretical: 869.063 Da |
Sequence | String: (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | helical reconstruction |
Aggregation state | filament |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.4 µm / Nominal defocus min: 1.8 µm / Nominal magnification: 105000 |
Sample stage | Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 34.2 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |