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- PDB-8q96: P301S Tau Filaments from the Brains of Tg2541 Transgenic Mouse Line -
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Open data
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Basic information
Entry | Database: PDB / ID: 8q96 | |||||||||
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Title | P301S Tau Filaments from the Brains of Tg2541 Transgenic Mouse Line | |||||||||
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![]() | PROTEIN FIBRIL / P301S tau / Frontotemporal dementia and parkinsonism linked to chromosome 17 / Transgenic mice / Electron cryo-microscopy | |||||||||
Function / homology | ![]() 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 | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3.09 Å | |||||||||
![]() | Schweighauser, M. / Murzin, A.G. / Macdonald, J. / Lavenir, I. / Crowther, R.A. / Scheres, S.H.W. / Goedert, M. | |||||||||
Funding support | ![]()
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![]() | ![]() 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
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 61.9 KB | Display | ![]() |
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PDB format | ![]() | 45.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.2 MB | Display | ![]() |
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Full document | ![]() | 1.2 MB | Display | |
Data in XML | ![]() | 20.8 KB | Display | |
Data in CIF | ![]() | 30.9 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 18269MC ![]() 8q92C M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 5961.934 Da / Num. of mol.: 4 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #2: Protein/peptide | Mass: 1039.273 Da / Num. of mol.: 4 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() #3: Protein/peptide | Mass: 869.063 Da / Num. of mol.: 4 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: FILAMENT / 3D reconstruction method: helical reconstruction |
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Sample preparation
Component | Name: P301S Tau Protein Filament (Tg2541) / Type: TISSUE Details: Human P301S tau filaments extracted from the brains of transgenic mouse line Tg2541 Entity ID: all / Source: NATURAL |
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Source (natural) | Organism: ![]() ![]() |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 105000 X / Nominal defocus max: 2400 nm / Nominal defocus min: 1800 nm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN |
Image recording | Electron dose: 34.2 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Helical symmerty | Angular rotation/subunit: -0.83 ° / Axial rise/subunit: 4.75 Å / Axial symmetry: C1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.09 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 22760 / Symmetry type: HELICAL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement | Resolution: 3.09→94.3 Å / Cor.coef. Fo:Fc: 0.873 / SU B: 15.854 / SU ML: 0.269 / ESU R: 0.163 Stereochemistry target values: MAXIMUM LIKELIHOOD WITH PHASES Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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Solvent computation | Solvent model: PARAMETERS FOR MASK CACLULATION | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 44.677 Å2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: 1 / Total: 525 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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