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Open data
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Basic information
Entry | Database: PDB / ID: 5o3t | ||||||||||||||||||||||||
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Title | Straight filament in Alzheimer's disease brain | ||||||||||||||||||||||||
![]() | Microtubule-associated protein tau | ||||||||||||||||||||||||
![]() | PROTEIN FIBRIL / TAU / AMYLOID / CROSS-BETA / BETA-HELIX | ||||||||||||||||||||||||
Function / homology | ![]() 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 / negative regulation of mitochondrial fission ...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 / negative regulation of mitochondrial fission / tubulin complex / phosphatidylinositol bisphosphate binding / main axon / regulation of long-term synaptic depression / negative regulation of kinase activity / negative regulation of tubulin deacetylation / generation of neurons / positive regulation of protein localization / 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 / microtubule polymerization / minor groove of adenine-thymine-rich DNA binding / lipoprotein particle binding / dynactin binding / glial cell projection / apolipoprotein binding / negative regulation of mitochondrial membrane potential / protein polymerization / axolemma / 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 / cytoplasmic microtubule organization / supramolecular fiber organization / regulation of cellular response to heat / stress granule assembly / positive regulation of superoxide anion generation / regulation of calcium-mediated signaling / axon cytoplasm / positive regulation of microtubule polymerization / somatodendritic compartment / synapse assembly / cellular response to brain-derived neurotrophic factor stimulus / astrocyte activation / phosphatidylinositol binding / nuclear periphery / cellular response to nerve growth factor stimulus / protein phosphatase 2A binding / regulation of autophagy / response to lead ion / synapse organization / microglial cell activation / cellular response to reactive oxygen species / Hsp90 protein binding / PKR-mediated signaling / protein homooligomerization / regulation of synaptic plasticity / memory / activation of cysteine-type endopeptidase activity involved in apoptotic process / microtubule cytoskeleton organization / SH3 domain binding / cytoplasmic ribonucleoprotein granule / microtubule cytoskeleton / neuron projection development / cell-cell signaling / double-stranded DNA binding / protein-macromolecule adaptor activity / single-stranded DNA binding / actin binding / protein-folding chaperone binding / cellular response to heat / cell body / growth cone / microtubule binding / sequence-specific DNA binding / amyloid fibril formation / microtubule / learning or memory / dendritic spine / 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 | ![]() | ||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3.4 Å | ||||||||||||||||||||||||
![]() | Fitzpatrick, A.W.P. / Falcon, B. / He, S. / Murzin, A.G. / Murshudov, G. / Garringer, H.G. / Crowther, R.A. / Ghetti, B. / Goedert, M. / Scheres, S.H.W. | ||||||||||||||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: Cryo-EM structures of tau filaments from Alzheimer's disease. Authors: Anthony W P Fitzpatrick / Benjamin Falcon / Shaoda He / Alexey G Murzin / Garib Murshudov / Holly J Garringer / R Anthony Crowther / Bernardino Ghetti / Michel Goedert / Sjors H W Scheres / ![]() ![]() Abstract: Alzheimer's disease is the most common neurodegenerative disease, and there are no mechanism-based therapies. The disease is defined by the presence of abundant neurofibrillary lesions and neuritic ...Alzheimer's disease is the most common neurodegenerative disease, and there are no mechanism-based therapies. The disease is defined by the presence of abundant neurofibrillary lesions and neuritic plaques in the cerebral cortex. Neurofibrillary lesions comprise paired helical and straight tau filaments, whereas tau filaments with different morphologies characterize other neurodegenerative diseases. No high-resolution structures of tau filaments are available. Here we present cryo-electron microscopy (cryo-EM) maps at 3.4-3.5 Å resolution and corresponding atomic models of paired helical and straight filaments from the brain of an individual with Alzheimer's disease. Filament cores are made of two identical protofilaments comprising residues 306-378 of tau protein, which adopt a combined cross-β/β-helix structure and define the seed for tau aggregation. Paired helical and straight filaments differ in their inter-protofilament packing, showing that they are ultrastructural polymorphs. These findings demonstrate that cryo-EM allows atomic characterization of amyloid filaments from patient-derived material, and pave the way for investigation of a range of neurodegenerative diseases. | ||||||||||||||||||||||||
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 233 KB | Display | ![]() |
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PDB format | ![]() | 190.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 905.9 KB | Display | ![]() |
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Full document | ![]() | 917.6 KB | Display | |
Data in XML | ![]() | 34.7 KB | Display | |
Data in CIF | ![]() | 50.3 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 3743MC ![]() 3741C ![]() 3742C ![]() 3744C ![]() 5o3lC ![]() 5o3oC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 7940.141 Da / Num. of mol.: 10 / Fragment: UNP Residues 623-695 / 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: TISSUE / 3D reconstruction method: helical reconstruction |
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Sample preparation
Component | Name: Tau / Type: TISSUE / Entity ID: all / Source: NATURAL |
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Source (natural) | Organism: ![]() |
Buffer solution | pH: 7.4 / Details: 20 mM Tris-HCl pH 7.4 containing 100 mM NaCl |
Specimen | Conc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: Sarkosyl-insoluble material was extracted from grey matter of frontal and temporal cortex from the patients brain, as described in the Methods section of the paper. |
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil Au 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 / Nominal defocus max: 3000 nm / Nominal defocus min: 900 nm / Calibrated defocus min: 900 nm / Calibrated defocus max: 3000 nm / Cs: 2.7 mm / C2 aperture diameter: 70 µm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 0.2 sec. / Electron dose: 1.2 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Num. of grids imaged: 1 / Num. of real images: 1560 Details: images were collected in movie-mode at 5 frames per second |
EM imaging optics | Energyfilter name: GIF Quantum / Energyfilter upper: 10 eV / Energyfilter lower: -10 eV |
Image scans | Width: 3710 / Height: 3710 / Movie frames/image: 50 |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||
Helical symmerty | Angular rotation/subunit: -1.05 ° / Axial rise/subunit: 4.74 Å / Axial symmetry: C1 | ||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 84701 | ||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 24689 / Num. of class averages: 1 / Symmetry type: HELICAL | ||||||||||||||||||||||||||||||||||||
Atomic model building | B value: 114 / Protocol: AB INITIO MODEL / Space: RECIPROCAL / Target criteria: Fourier shell correlation Details: Fourier-space refinement of the complete atomic model against the paired helical filament and straight filament maps was performed in REFMAC. A stack of three consecutive monomers from each ...Details: Fourier-space refinement of the complete atomic model against the paired helical filament and straight filament maps was performed in REFMAC. A stack of three consecutive monomers from each of the protofilaments was refined to preserve nearest-neighbour interactions for the middle chain. | ||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 2RNM Pdb chain-ID: A / Accession code: 2RNM / Pdb chain residue range: 226-242 / Source name: PDB / Type: experimental model |