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Yorodumi- EMDB-13740: Tomogram of a TauRD-YFP aggregate in a TauRD-YFP expressing prima... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-13740 | ||||||||||||
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Title | Tomogram of a TauRD-YFP aggregate in a TauRD-YFP expressing primary mouse neuron | ||||||||||||
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Sample |
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Biological species | Mus musculus (house mouse) | ||||||||||||
Method | electron tomography / cryo EM | ||||||||||||
Authors | Trinkaus V-A / Saha I / Fernandez-Busnadiego R / Hartl F-U | ||||||||||||
Funding support | Germany, 3 items
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Citation | Journal: Nat Commun / Year: 2023 Title: The AAA+ chaperone VCP disaggregates Tau fibrils and generates aggregate seeds in a cellular system. Authors: Itika Saha / Patricia Yuste-Checa / Miguel Da Silva Padilha / Qiang Guo / Roman Körner / Hauke Holthusen / Victoria A Trinkaus / Irina Dudanova / Rubén Fernández-Busnadiego / Wolfgang ...Authors: Itika Saha / Patricia Yuste-Checa / Miguel Da Silva Padilha / Qiang Guo / Roman Körner / Hauke Holthusen / Victoria A Trinkaus / Irina Dudanova / Rubén Fernández-Busnadiego / Wolfgang Baumeister / David W Sanders / Saurabh Gautam / Marc I Diamond / F Ulrich Hartl / Mark S Hipp / Abstract: Amyloid-like aggregates of the microtubule-associated protein Tau are associated with several neurodegenerative disorders including Alzheimer's disease. The existence of cellular machinery for the ...Amyloid-like aggregates of the microtubule-associated protein Tau are associated with several neurodegenerative disorders including Alzheimer's disease. The existence of cellular machinery for the removal of such aggregates has remained unclear, as specialized disaggregase chaperones are thought to be absent in mammalian cells. Here we show in cell culture and in neurons that the hexameric ATPase valosin-containing protein (VCP) is recruited to ubiquitylated Tau fibrils, resulting in their efficient disaggregation. Aggregate clearance depends on the functional cooperation of VCP with heat shock 70 kDa protein (Hsp70) and the ubiquitin-proteasome machinery. While inhibition of VCP activity stabilizes large Tau aggregates, disaggregation by VCP generates seeding-active Tau species as byproduct. These findings identify VCP as a core component of the machinery for the removal of neurodegenerative disease aggregates and suggest that its activity can be associated with enhanced aggregate spreading in tauopathies. | ||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_13740.map.gz | 634.6 MB | EMDB map data format | |
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Header (meta data) | emd-13740-v30.xml emd-13740.xml | 9.6 KB 9.6 KB | Display Display | EMDB header |
Images | emd_13740.png | 220.1 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-13740 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-13740 | HTTPS FTP |
-Validation report
Summary document | emd_13740_validation.pdf.gz | 447.8 KB | Display | EMDB validaton report |
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Full document | emd_13740_full_validation.pdf.gz | 447.4 KB | Display | |
Data in XML | emd_13740_validation.xml.gz | 4.6 KB | Display | |
Data in CIF | emd_13740_validation.cif.gz | 5.1 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-13740 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-13740 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_13740.map.gz / Format: CCP4 / Size: 686.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. generated in cubic-lattice coordinate | ||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 14.08 Å | ||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
-Entire : Tomogram of a TauRD-YFP aggregate in a TauRD-YFP expressing prima...
Entire | Name: Tomogram of a TauRD-YFP aggregate in a TauRD-YFP expressing primary mouse neuron |
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Components |
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-Supramolecule #1: Tomogram of a TauRD-YFP aggregate in a TauRD-YFP expressing prima...
Supramolecule | Name: Tomogram of a TauRD-YFP aggregate in a TauRD-YFP expressing primary mouse neuron type: cell / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Mus musculus (house mouse) / Organ: brain |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | electron tomography |
Aggregation state | cell |
-Sample preparation
Buffer | pH: 7.2 |
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Vitrification | Cryogen name: ETHANE-PROPANE |
Sectioning | Focused ion beam - Instrument: OTHER / Focused ion beam - Ion: OTHER / Focused ion beam - Voltage: 30 kV / Focused ion beam - Current: 0.1 nA / Focused ion beam - Duration: 1800 sec. / Focused ion beam - Temperature: 90 K / Focused ion beam - Initial thickness: 1000 nm / Focused ion beam - Final thickness: 100 nm Focused ion beam - Details: The value given for _em_focused_ion_beam.instrument is FIB Quanta. This is not in a list of allowed values {'DB235', 'OTHER'} so OTHER is written into the XML file. |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 110.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 6.0 µm / Nominal defocus min: 5.0 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Final reconstruction | Number images used: 56 |
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