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.
A: 15593.84 Å / B: 15593.84 Å / C: 1448.24 Å α=β=γ: 90.0 °
-
Supplemental data
-
Sample components
-
Entire : Tomogram of a TauRD-YFP aggregate in a TauRD-YFP expressing Hek29...
Entire
Name: Tomogram of a TauRD-YFP aggregate in a TauRD-YFP expressing Hek293T cell
Components
Cell: Tomogram of a TauRD-YFP aggregate in a TauRD-YFP expressing Hek293T cell
-
Supramolecule #1: Tomogram of a TauRD-YFP aggregate in a TauRD-YFP expressing Hek29...
Supramolecule
Name: Tomogram of a TauRD-YFP aggregate in a TauRD-YFP expressing Hek293T cell type: cell / ID: 1 / Parent: 0
Source (natural)
Organism: Homo sapiens (human) / Organ: Kidney
-
Experimental details
-
Structure determination
Method
cryo EM
Processing
electron tomography
Aggregation state
cell
-
Sample preparation
Buffer
pH: 7.2
Vitrification
Cryogen name: ETHANE
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
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron optics
Illumination mode: OTHER / Imaging mode: BRIGHT FIELDBright-field microscopy
Specialist optics
Phase plate: VOLTA PHASE PLATE
Image recording
Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 110.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
-
Image processing
Final reconstruction
Number images used: 60
+
About Yorodumi
-
News
-
Feb 9, 2022. New format data for meta-information of EMDB entries
New format data for meta-information of EMDB entries
Version 3 of the EMDB header file is now the official format.
The previous official version 1.9 will be removed from the archive.
In the structure databanks used in Yorodumi, some data are registered as the other names, "COVID-19 virus" and "2019-nCoV". Here are the details of the virus and the list of structure data.
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)
EMDB accession codes are about to change! (news from PDBe EMDB page)
The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
The EM Navigator/Yorodumi systems omit the EMD- prefix.
Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator
Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.
Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi
Movie
Controller
Yorodumi
Open data
Basic information
Map data
Sample
Homo sapiens (human)
Authors
Germany, 3 items 
Citation
Structure visualization
Downloads & links
EMDB map data format
emd_13739.png
http://ftp.pdbj.org/pub/emdb/structures/EMD-13739
Z (Sec.)
Y (Row.)
X (Col.)
Sample components
Processing
Electron microscopy
