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Yorodumi- PDB-7mkf: Paired helical tau filament extracted from PrP-CAA Patient brain ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7mkf | ||||||
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Title | Paired helical tau filament extracted from PrP-CAA Patient brain tissue | tau filament | PHF Tau | ||||||
Components | Isoform Tau-F of Microtubule-associated protein tau | ||||||
Keywords | PROTEIN FIBRIL / tau filament / GSS / PrP-CAA / amyloid fibril / Alzheimer disease | ||||||
Function / homology | Activation of AMPK downstream of NMDARs / PKR-mediated signaling / Isoform Tau-F of Microtubule-associated protein tau Function and homology information | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 3 Å | ||||||
Authors | Hoq, M.R. | ||||||
Funding support | United States, 1items
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Citation | Journal: Acta Neuropathol / Year: 2021 Title: Structure of Tau filaments in Prion protein amyloidoses. Authors: Grace I Hallinan / Md Rejaul Hoq / Manali Ghosh / Frank S Vago / Anllely Fernandez / Holly J Garringer / Ruben Vidal / Wen Jiang / Bernardino Ghetti / Abstract: In human neurodegenerative diseases associated with the intracellular aggregation of Tau protein, the ordered cores of Tau filaments adopt distinct folds. Here, we analyze Tau filaments isolated from ...In human neurodegenerative diseases associated with the intracellular aggregation of Tau protein, the ordered cores of Tau filaments adopt distinct folds. Here, we analyze Tau filaments isolated from the brain of individuals affected by Prion-Protein cerebral amyloid angiopathy (PrP-CAA) with a nonsense mutation in the PRNP gene that leads to early termination of translation of PrP (Q160Ter or Q160X), and Gerstmann-Sträussler-Scheinker (GSS) disease, with a missense mutation in the PRNP gene that leads to an amino acid substitution at residue 198 (F198S) of PrP. The clinical and neuropathologic phenotypes associated with these two mutations in PRNP are different; however, the neuropathologic analyses of these two genetic variants have consistently shown the presence of numerous neurofibrillary tangles (NFTs) made of filamentous Tau aggregates in neurons. We report that Tau filaments in PrP-CAA (Q160X) and GSS (F198S) are composed of 3-repeat and 4-repeat Tau isoforms, having a striking similarity to NFTs in Alzheimer disease (AD). In PrP-CAA (Q160X), Tau filaments are made of both paired helical filaments (PHFs) and straight filaments (SFs), while in GSS (F198S), only PHFs were found. Mass spectrometry analyses of Tau filaments extracted from PrP-CAA (Q160X) and GSS (F198S) brains show the presence of post-translational modifications that are comparable to those seen in Tau aggregates from AD. Cryo-EM analysis reveals that the atomic models of the Tau filaments obtained from PrP-CAA (Q160X) and GSS (F198S) are identical to those of the Tau filaments from AD, and are therefore distinct from those of Pick disease, chronic traumatic encephalopathy, and corticobasal degeneration. Our data support the hypothesis that in the presence of extracellular amyloid deposits and regardless of the primary amino acid sequence of the amyloid protein, similar molecular mechanisms are at play in the formation of identical Tau filaments. | ||||||
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 | 7mkf.cif.gz | 308.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7mkf.ent.gz | 233.6 KB | Display | PDB format |
PDBx/mmJSON format | 7mkf.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7mkf_validation.pdf.gz | 873.1 KB | Display | wwPDB validaton report |
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Full document | 7mkf_full_validation.pdf.gz | 874.4 KB | Display | |
Data in XML | 7mkf_validation.xml.gz | 30 KB | Display | |
Data in CIF | 7mkf_validation.cif.gz | 41.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/mk/7mkf ftp://data.pdbj.org/pub/pdb/validation_reports/mk/7mkf | HTTPS FTP |
-Related structure data
Related structure data | 23871MC 7mkgC 7mkhC 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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-Components
#1: Protein | Mass: 45919.871 Da / Num. of mol.: 10 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / References: UniProt: P10636-8 |
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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: Paired helical filament (PHF) from PrP-CAA / Type: ORGANELLE OR CELLULAR COMPONENT Details: PHF tau in PrP-CAA, caused by the Q160X truncating mutation in PRNP Entity ID: all / Source: NATURAL |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Buffer solution | pH: 7.4 |
Specimen | Conc.: 1 mg/ml / 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: TFS KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 1.067 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of real images: 2004 |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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Helical symmerty | Angular rotation/subunit: -1.2 ° / Axial rise/subunit: 4.77 Å / Axial symmetry: C1 |
3D reconstruction | Resolution: 3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 60 / Symmetry type: HELICAL |