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Open data
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Basic information
Entry | Database: PDB / ID: 6vi3 | |||||||||
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Title | Straight Filament from Alzheimer's Disease Human Brain Tissue | |||||||||
![]() | Microtubule-associated protein tau | |||||||||
![]() | PROTEIN FIBRIL / Pathological amyloid fibril cross-beta fold parallel beta-sheets | |||||||||
Function / homology | ![]() plus-end-directed organelle transport along microtubule / axonal transport / histone-dependent DNA binding / neurofibrillary tangle assembly / positive regulation of diacylglycerol kinase activity / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / positive regulation of protein localization to synapse / microtubule lateral binding / tubulin complex ...plus-end-directed organelle transport along microtubule / axonal transport / histone-dependent DNA binding / neurofibrillary tangle assembly / positive regulation of diacylglycerol kinase activity / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / positive regulation of protein localization to synapse / microtubule lateral binding / 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 / regulation of chromosome organization / positive regulation of protein localization / rRNA metabolic process / internal protein amino acid acetylation / regulation of mitochondrial fission / intracellular distribution of mitochondria / axonal transport of mitochondrion / 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 / apolipoprotein binding / glial cell projection / negative regulation of mitochondrial membrane potential / protein polymerization / negative regulation of mitochondrial fission / 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 / supramolecular fiber organization / regulation of cellular response to heat / stress granule assembly / cytoplasmic microtubule organization / regulation of calcium-mediated signaling / axon cytoplasm / positive regulation of microtubule polymerization / somatodendritic compartment / cellular response to brain-derived neurotrophic factor stimulus / synapse assembly / phosphatidylinositol binding / nuclear periphery / cellular response to nerve growth factor stimulus / positive regulation of superoxide anion generation / protein phosphatase 2A binding / regulation of autophagy / astrocyte activation / response to lead ion / synapse organization / microglial cell activation / Hsp90 protein binding / regulation of synaptic plasticity / PKR-mediated signaling / protein homooligomerization / memory / cytoplasmic ribonucleoprotein granule / cellular response to reactive oxygen species / SH3 domain binding / microtubule cytoskeleton organization / activation of cysteine-type endopeptidase activity involved in apoptotic process / neuron projection development / microtubule cytoskeleton / cell-cell signaling / protein-macromolecule adaptor activity / actin binding / single-stranded DNA binding / cellular response to heat / protein-folding chaperone binding / cell body / growth cone / microtubule binding / double-stranded DNA binding / microtubule / amyloid fibril formation / sequence-specific DNA binding / dendritic spine / learning or memory / 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: 3.3 Å | |||||||||
![]() | Arakhamia, T. / Lee, C.E. / Carlomagno, Y. / Duong, D.M. / Kundinger, S.R. / Wang, K. / Williams, D. / DeTure, M. / Dickson, D.W. / Cook, C.N. ...Arakhamia, T. / Lee, C.E. / Carlomagno, Y. / Duong, D.M. / Kundinger, S.R. / Wang, K. / Williams, D. / DeTure, M. / Dickson, D.W. / Cook, C.N. / Seyfried, N.T. / Petrucelli, L. / Fitzpatrick, A.W.P. | |||||||||
Funding support | ![]()
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![]() | ![]() 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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Remark 0 | THIS ENTRY 6VI3 REFLECTS AN ALTERNATIVE MODELING OF THE ORIGINAL DATA IN EMD-0260, DETERMINED BY ...THIS ENTRY 6VI3 REFLECTS AN ALTERNATIVE MODELING OF THE ORIGINAL DATA IN EMD-0260, DETERMINED BY Falcon, B. et al. |
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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 | ![]() | 36.5 KB | Display | ![]() |
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PDB format | ![]() | 24.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.3 MB | Display | ![]() |
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Full document | ![]() | 1.3 MB | Display | |
Data in XML | ![]() | 23.1 KB | Display | |
Data in CIF | ![]() | 31.1 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 0260M ![]() 6vh7C ![]() 6vhaC ![]() 6vhlC M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 8370.578 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #2: Chemical | Has ligand of interest | Y | |
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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: Straight Filament from Alzheimer's Disease Human Brain Tissue Type: TISSUE / Entity ID: #1 / 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 |
Specimen support | Details: unspecified |
Vitrification | Cryogen name: ETHANE |
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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 | Electron dose: 60 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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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: 62782 / Symmetry type: HELICAL |