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Open data
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Basic information
Entry | Database: PDB / ID: 6nwp | |||||||||||||||||||||
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Title | Chronic traumatic encephalopathy Type I Tau filament | |||||||||||||||||||||
![]() | Microtubule-associated protein tau![]() | |||||||||||||||||||||
![]() | PROTEIN FIBRIL / Tau / ![]() ![]() ![]() | |||||||||||||||||||||
Function / homology | ![]() plus-end-directed organelle transport along microtubule / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||||||||||||||
Biological species | ![]() ![]() | |||||||||||||||||||||
Method | ![]() ![]() | |||||||||||||||||||||
![]() | Falcon, B. / Zivanov, J. / Zhang, W. / Murzin, A.G. / Garringer, H.J. / Vidal, R. / Crowther, R.A. / Newell, K.L. / Ghetti, B. / Goedert, M. / Scheres, H.W. | |||||||||||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: Novel tau filament fold in chronic traumatic encephalopathy encloses hydrophobic molecules. Authors: Benjamin Falcon / Jasenko Zivanov / Wenjuan Zhang / Alexey G Murzin / Holly J Garringer / Ruben Vidal / R Anthony Crowther / Kathy L Newell / Bernardino Ghetti / Michel Goedert / Sjors H W Scheres / ![]() ![]() Abstract: Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy that is associated with repetitive head impacts or exposure to blast waves. First described as punch-drunk syndrome and ...Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy that is associated with repetitive head impacts or exposure to blast waves. First described as punch-drunk syndrome and dementia pugilistica in retired boxers, CTE has since been identified in former participants of other contact sports, ex-military personnel and after physical abuse. No disease-modifying therapies currently exist, and diagnosis requires an autopsy. CTE is defined by an abundance of hyperphosphorylated tau protein in neurons, astrocytes and cell processes around blood vessels. This, together with the accumulation of tau inclusions in cortical layers II and III, distinguishes CTE from Alzheimer's disease and other tauopathies. However, the morphologies of tau filaments in CTE and the mechanisms by which brain trauma can lead to their formation are unknown. Here we determine the structures of tau filaments from the brains of three individuals with CTE at resolutions down to 2.3 Å, using cryo-electron microscopy. We show that filament structures are identical in the three cases but are distinct from those of Alzheimer's and Pick's diseases, and from those formed in vitro. Similar to Alzheimer's disease, all six brain tau isoforms assemble into filaments in CTE, and residues K274-R379 of three-repeat tau and S305-R379 of four-repeat tau form the ordered core of two identical C-shaped protofilaments. However, a different conformation of the β-helix region creates a hydrophobic cavity that is absent in tau filaments from the brains of patients with Alzheimer's disease. This cavity encloses an additional density that is not connected to tau, which suggests that the incorporation of cofactors may have a role in tau aggregation in CTE. Moreover, filaments in CTE have distinct protofilament interfaces to those of Alzheimer's disease. Our structures provide a unifying neuropathological criterion for CTE, and support the hypothesis that the formation and propagation of distinct conformers of assembled tau underlie different neurodegenerative diseases. | |||||||||||||||||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 127.7 KB | Display | ![]() |
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PDB format | ![]() | 90.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 0527MC ![]() 0528C ![]() 6nwqC M: map data used to model this data C: citing same article ( |
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Similar structure data | |
EM raw data | ![]() Data size: 9.7 TB / Data #1: Raw Movies [micrographs - multiframe] / Data #2: Aligned Micrographs [micrographs - single frame]) |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | ![]() Mass: 45919.871 Da / Num. of mol.: 6 / Source method: isolated from a natural source / Source: (natural) ![]() ![]() ![]() #2: Water | ChemComp-HOH / | ![]() |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: TISSUE / 3D reconstruction method: helical reconstruction |
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Sample preparation
Component | Name: Tau filaments extracted from the temporal cortex of a patient with chronic traumatic encephalopathy Type: TISSUE / Entity ID: #1 / Source: NATURAL | ||||||||||||
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Source (natural) | Organism: ![]() ![]() | ||||||||||||
Buffer solution | pH: 7.4 | ||||||||||||
Buffer component |
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Specimen | Conc.: 0.5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() | ||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 | ||||||||||||
Vitrification![]() | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 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![]() ![]() |
Image recording | Average exposure time: 9 sec. / Electron dose: 55.48 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
EM imaging optics | Energyfilter name![]() |
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Processing
EM software |
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CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||
Helical symmerty | Angular rotation/subunit: 179.4 ° / Axial rise/subunit: 2.37 Å / Axial symmetry: C1 | ||||||||||||||||||||
3D reconstruction![]() | Resolution: 2.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 113178 / Symmetry type: HELICAL | ||||||||||||||||||||
Atomic model building | B value: 51.7 / Space: RECIPROCAL / Target criteria: Fourier shell correlation Details: Fourier-space refinement of the complete atomic model against the chronic traumatic encephalopathy Type I Tau filament map was performed in REFMAC. A stack of three consecutive monomers was ...Details: Fourier-space refinement of the complete atomic model against the chronic traumatic encephalopathy Type I Tau filament map was performed in REFMAC. A stack of three consecutive monomers was refined to preserve nearest-neighbour interactions for the middle chain. |