- EMDB-18269: P301S Tau Filaments from the Brains of Tg2541 Transgenic Mouse Line -
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Basic information
Entry
Database: EMDB / ID: EMD-18269
Title
P301S Tau Filaments from the Brains of Tg2541 Transgenic Mouse Line
Map data
Sample
Tissue: P301S Tau Protein Filament (Tg2541)
Protein or peptide: Isoform Tau-E of Microtubule-associated protein tau
Protein or peptide: Unknown protein
Protein or peptide: Unknown protein
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 / intrinsic apoptotic signaling pathway in response to oxidative stress ...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 / intrinsic apoptotic signaling pathway in response to oxidative stress / tubulin complex / main axon / negative regulation of tubulin deacetylation / axoneme / glial cell projection / : / intracellular transport / mRNA transport / positive regulation of axon extension / axonal growth cone / response to nutrient / regulation of cellular response to heat / positive regulation of microtubule polymerization / heat shock protein binding / axonogenesis / protein phosphatase 2A binding / regulation of autophagy / response to lead ion / neuron migration / Hsp90 protein binding / cytoplasmic side of plasma membrane / positive regulation of neuron projection development / microtubule cytoskeleton organization / microtubule cytoskeleton / neuron projection development / protein-folding chaperone binding / cell body / growth cone / microtubule binding / microtubule / postsynaptic density / neuron projection / membrane raft / axon / neuronal cell body / DNA damage response / dendrite / protein-containing complex binding / protein kinase binding / enzyme binding / DNA binding / extracellular region / nucleus / plasma membrane / cytoplasm / cytosol Similarity search - Function
: / 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. Similarity search - Domain/homology
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.
Protein or peptide: Isoform Tau-E of Microtubule-associated protein tau
Protein or peptide: Unknown protein
Protein or peptide: Unknown protein
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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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