+Open data
-Basic information
Entry | Database: PDB / ID: 9cgz | ||||||
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Title | Alzheimer's Disease Seeded Mixed 0N4R and 0N3R Tau Fibrils | ||||||
Components | Isoform Fetal-tau of Microtubule-associated protein tau | ||||||
Keywords | PROTEIN FIBRIL / Tau / Amyloid / Cross-beta / Seeded-Fibril | ||||||
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 / tubulin complex ...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 / 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 / rRNA metabolic process / internal protein amino acid acetylation / regulation of chromosome organization / regulation of mitochondrial fission / axonal transport of mitochondrion / axon development / intracellular distribution of mitochondria / central nervous system neuron development / regulation of microtubule polymerization / microtubule polymerization / lipoprotein particle binding / minor groove of adenine-thymine-rich DNA binding / dynactin binding / glial cell projection / negative regulation of mitochondrial membrane potential / apolipoprotein binding / protein polymerization / axolemma / negative regulation of mitochondrial fission / 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 / positive regulation of protein localization / regulation of cellular response to heat / cytoplasmic microtubule organization / stress granule assembly / supramolecular fiber organization / regulation of calcium-mediated signaling / axon cytoplasm / somatodendritic compartment / positive regulation of microtubule polymerization / 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 / microglial cell activation / synapse organization / Hsp90 protein binding / protein homooligomerization / PKR-mediated signaling / regulation of synaptic plasticity / memory / activation of cysteine-type endopeptidase activity involved in apoptotic process / microtubule cytoskeleton organization / SH3 domain binding / cellular response to reactive oxygen species / cytoplasmic ribonucleoprotein granule / microtubule cytoskeleton / neuron projection development / cell-cell signaling / protein-macromolecule adaptor activity / protein-folding chaperone binding / single-stranded DNA binding / actin binding / cellular response to heat / cell body / 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 / dendrite / DNA damage response / protein kinase binding / enzyme binding / mitochondrion / DNA binding Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 2.69 Å | ||||||
Authors | Duan, P. / Dregni, A.J. / Xu, H. / Changolkar, L. / Lee, V.M.-Y. / Hong, M. | ||||||
Funding support | United States, 1items
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Citation | Journal: J Biol Chem / Year: 2024 Title: Alzheimer's disease seeded tau forms paired helical filaments yet lacks seeding potential. Authors: Pu Duan / Aurelio J Dregni / Hong Xu / Lakshmi Changolkar / Virginia M-Y Lee / Edward B Lee / Mei Hong / Abstract: Alzheimer's disease (AD) and many other neurodegenerative diseases are characterized by pathological aggregation of the protein tau. These tau aggregates spread in a stereotypical spatiotemporal ...Alzheimer's disease (AD) and many other neurodegenerative diseases are characterized by pathological aggregation of the protein tau. These tau aggregates spread in a stereotypical spatiotemporal pattern in the brain of each disease, suggesting that the misfolded tau can recruit soluble monomers to adopt the same pathological structure. To investigate whether recruited tau indeed adopts the same structure and properties as the original seed, here we template recombinant full-length 0N3R tau, 0N4R tau, and an equimolar mixture of the two using sarkosyl-insoluble tau extracted from AD brain and determine the structures of the resulting fibrils using cryoelectron microscopy. We show that these cell-free amplified tau fibrils adopt the same molecular structure as the AD paired-helical filament (PHF) tau but are unable to template additional monomers. Therefore, the PHF structure alone is insufficient for defining the pathological properties of AD tau, and other biochemical components such as tau posttranslational modifications, other proteins, polyanionic cofactors, and salt are required for the prion-like serial propagation of tauopathies. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 9cgz.cif.gz | 169.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb9cgz.ent.gz | 122.7 KB | Display | PDB format |
PDBx/mmJSON format | 9cgz.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 9cgz_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 9cgz_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 9cgz_validation.xml.gz | 32.5 KB | Display | |
Data in CIF | 9cgz_validation.cif.gz | 45.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/cg/9cgz ftp://data.pdbj.org/pub/pdb/validation_reports/cg/9cgz | HTTPS FTP |
-Related structure data
Related structure data | 45589MC 9cgxC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 36821.121 Da / Num. of mol.: 6 Source method: isolated from a genetically manipulated source Details: Mixture of 0N4R and 0N3R monomers templated by Alzheimer's Disease Seeds 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: Amyloid Fibril of Mixed 0N4R and 0N3R Tau Seeded with Alzheimer's Disease Tau from Human Brain 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 | Conc.: 1.6 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Instrument: FEI VITROBOT MARK I / 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: SPOT SCAN |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 81000 X / Nominal defocus max: 2000 nm / Nominal defocus min: 200 nm / Cs: 2.7 mm / C2 aperture diameter: 100 µm |
Specimen holder | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 2.25 sec. / Electron dose: 45.7 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 7917 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||
Helical symmerty | Angular rotation/subunit: 179.51 ° / Axial rise/subunit: 2.376 Å / Axial symmetry: C1 | ||||||||||||||||||||
Particle selection | Num. of particles selected: 2966238 | ||||||||||||||||||||
3D reconstruction | Resolution: 2.69 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 55886 / Symmetry type: HELICAL |