+Open data
-Basic information
Entry | Database: PDB / ID: 6hrf | ||||||||||||||||||
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Title | Straight filament from sporadic Alzheimer's disease brain | ||||||||||||||||||
Components | Microtubule-associated protein tau | ||||||||||||||||||
Keywords | PROTEIN FIBRIL / Tau / helical / filament / fibril / amyloid / Alzheimer's disease / SF / straight filament / NFT / neurofibrillary tangly | ||||||||||||||||||
Function / homology | Function and homology information 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 | Homo sapiens (human) | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3.3 Å | ||||||||||||||||||
Authors | Falcon, B. / Zhang, W. / Schweighauser, M. / Murzin, A.G. / Vidal, R. / Garringer, H.J. / Ghetti, B. / Scheres, S.H.W. / Goedert, M. | ||||||||||||||||||
Funding support | United Kingdom, United States, 5items
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Citation | Journal: Acta Neuropathol / Year: 2018 Title: Tau filaments from multiple cases of sporadic and inherited Alzheimer's disease adopt a common fold. Authors: Benjamin Falcon / Wenjuan Zhang / Manuel Schweighauser / Alexey G Murzin / Ruben Vidal / Holly J Garringer / Bernardino Ghetti / Sjors H W Scheres / Michel Goedert / Abstract: The ordered assembly of tau protein into abnormal filaments is a defining characteristic of Alzheimer's disease (AD) and other neurodegenerative disorders. It is not known if the structures of tau ...The ordered assembly of tau protein into abnormal filaments is a defining characteristic of Alzheimer's disease (AD) and other neurodegenerative disorders. It is not known if the structures of tau filaments vary within, or between, the brains of individuals with AD. We used a combination of electron cryo-microscopy (cryo-EM) and immuno-gold negative-stain electron microscopy (immuno-EM) to determine the structures of paired helical filaments (PHFs) and straight filaments (SFs) from the frontal cortex of 17 cases of AD (15 sporadic and 2 inherited) and 2 cases of atypical AD (posterior cortical atrophy). The high-resolution structures of PHFs and SFs from the frontal cortex of 3 cases of AD, 2 sporadic and 1 inherited, were determined by cryo-EM. We also used immuno-EM to study the PHFs and SFs from a number of cortical and subcortical brain regions. PHFs outnumbered SFs in all AD cases. By cryo-EM, PHFs and SFs were made of two C-shaped protofilaments with a combined cross-β/β-helix structure, as described previously for one case of AD. The higher resolution structures obtained here showed two additional amino acids at each end of the protofilament. The immuno-EM findings, which indicated the presence of repeats 3 and 4, but not of the N-terminal regions of repeats 1 and 2, of tau in the filament cores of all AD cases, were consistent with the cryo-EM results. These findings show that there is no significant variation in tau filament structures between individuals with AD. This knowledge will be crucial for understanding the mechanisms that underlie tau filament formation and for developing novel diagnostics and therapies. | ||||||||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6hrf.cif.gz | 125.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6hrf.ent.gz | 83.2 KB | Display | PDB format |
PDBx/mmJSON format | 6hrf.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6hrf_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 6hrf_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 6hrf_validation.xml.gz | 28.8 KB | Display | |
Data in CIF | 6hrf_validation.cif.gz | 39.8 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/hr/6hrf ftp://data.pdbj.org/pub/pdb/validation_reports/hr/6hrf | HTTPS FTP |
-Related structure data
Related structure data | 0260MC 0259C 6hreC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data |
-Links
-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) Homo sapiens (human) / Tissue: Brain / References: UniProt: P10636 |
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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 |
-Sample preparation
Component | Name: Tau filaments extracted from the frontotemporal cortex of a patient with sporadic Alzheimer's disease Type: TISSUE / Entity ID: all / Source: NATURAL | ||||||||||||
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Source (natural) | Organism: Homo sapiens (human) / Organ: Brain / Tissue: Frontotemporal cortex | ||||||||||||
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: NO / Vitrification applied: YES / Details: Dispersed filaments | ||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2800 nm / Nominal defocus min: 1700 nm / Cs: 2.7 mm |
Image recording | Electron dose: 1.2 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 QUANTUM (4k x 4k) |
EM imaging optics | Energyfilter name: GIF Quantum LS |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Helical symmerty | Angular rotation/subunit: -1.04 ° / Axial rise/subunit: 4.76 Å / Axial symmetry: C1 | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 27103 / Symmetry type: HELICAL | ||||||||||||||||||||||||
Atomic model building | B value: 82 / Protocol: AB INITIO MODEL / Space: RECIPROCAL / Target criteria: Fourier shell correlation Details: Fourier-space refinement of the complete atomic model against the narrow Pick filament map was performed in REFMAC. A stack of three consecutive monomers was refined to preserve nearest- ...Details: Fourier-space refinement of the complete atomic model against the narrow Pick filament map was performed in REFMAC. A stack of three consecutive monomers was refined to preserve nearest-neighbour interactions for the middle chain. |