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Yorodumi- PDB-7qjw: In vitro assembled tau filaments with structures like chronic tra... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7qjw | ||||||
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Title | In vitro assembled tau filaments with structures like chronic traumatic encephalopathy type II (8a) | ||||||
Components | Microtubule-associated protein tauTau protein | ||||||
Keywords | PROTEIN FIBRIL / Alzheimer's Disease / Amyloid / Tau / Neurodegeneration / Chronic traumatic encephalopathy | ||||||
Function / homology | Function and homology information 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 / glial cell projection / negative regulation of mitochondrial membrane potential / apolipoprotein binding / 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 / Activation of AMPK downstream of NMDARs / regulation of microtubule cytoskeleton organization / supramolecular fiber organization / stress granule assembly / regulation of cellular response to heat / cytoplasmic microtubule organization / regulation of calcium-mediated signaling / positive regulation of microtubule polymerization / axon cytoplasm / 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 / cellular response to reactive oxygen species / microtubule cytoskeleton organization / SH3 domain binding / cytoplasmic ribonucleoprotein granule / 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 / cell body / protein-folding chaperone binding / growth cone / microtubule binding / double-stranded DNA binding / microtubule / sequence-specific DNA binding / amyloid fibril formation / 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 | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 2.81 Å | ||||||
Authors | Lovestam, S. / Scheres, S.H.W. | ||||||
Funding support | United Kingdom, 1items
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Citation | Journal: Elife / Year: 2022 Title: Assembly of recombinant tau into filaments identical to those of Alzheimer's disease and chronic traumatic encephalopathy. Authors: Sofia Lövestam / Fujiet Adrian Koh / Bart van Knippenberg / Abhay Kotecha / Alexey G Murzin / Michel Goedert / Sjors H W Scheres / Abstract: Abundant filamentous inclusions of tau are characteristic of more than 20 neurodegenerative diseases that are collectively termed tauopathies. Electron cryo-microscopy (cryo-EM) structures of tau ...Abundant filamentous inclusions of tau are characteristic of more than 20 neurodegenerative diseases that are collectively termed tauopathies. Electron cryo-microscopy (cryo-EM) structures of tau amyloid filaments from human brain revealed that distinct tau folds characterise many different diseases. A lack of laboratory-based model systems to generate these structures has hampered efforts to uncover the molecular mechanisms that underlie tauopathies. Here, we report in vitro assembly conditions with recombinant tau that replicate the structures of filaments from both Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE), as determined by cryo-EM. Our results suggest that post-translational modifications of tau modulate filament assembly, and that previously observed additional densities in AD and CTE filaments may arise from the presence of inorganic salts, like phosphates and sodium chloride. In vitro assembly of tau into disease-relevant filaments will facilitate studies to determine their roles in different diseases, as well as the development of compounds that specifically bind to these structures or prevent their formation. | ||||||
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 | 7qjw.cif.gz | 190.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7qjw.ent.gz | 148.5 KB | Display | PDB format |
PDBx/mmJSON format | 7qjw.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qj/7qjw ftp://data.pdbj.org/pub/pdb/validation_reports/qj/7qjw | HTTPS FTP |
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-Related structure data
Related structure data | 14024MC 7qjvC 7qjxC 7qjyC 7qjzC 7qk1C 7qk2C 7qk3C 7qk5C 7qk6C 7qkfC 7qkgC 7qkhC 7qkiC 7qkjC 7qkkC 7qklC 7qkmC 7qkuC 7qkvC 7qkwC 7qkxC 7qkyC 7qkzC 7ql0C 7ql1C 7ql2C 7ql3C 7ql4C 7r4tC 7r5hC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 45919.871 Da / Num. of mol.: 6 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: MAPT, MAPTL, MTBT1, TAU / Production host: Escherichia coli (E. coli) / References: UniProt: P10636 |
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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 |
-Sample preparation
Component | Name: Tau / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Escherichia coli (E. coli) |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-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 FIELDBright-field microscopy / Nominal defocus max: 3500 nm / Nominal defocus min: 1000 nm |
Image recording | Electron dose: 40 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
-Processing
EM software | Name: RELION / Version: 4 / Category: 3D reconstruction / Details: Amazing programme |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
Helical symmerty | Angular rotation/subunit: 179.44 ° / Axial rise/subunit: 2.43 Å / Axial symmetry: C1 |
3D reconstruction | Resolution: 2.81 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 56911 / Symmetry type: HELICAL |
Atomic model building | Protocol: AB INITIO MODEL |