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Yorodumi- EMDB-23894: Paired helical tau filament extracted from GSS Patient brain tiss... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-23894 | |||||||||
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Title | Paired helical tau filament extracted from GSS Patient brain tissue | tau filament from Gerstmann Straussler Scheinker disease | PHF Tau | |||||||||
Map data | ||||||||||
Sample |
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Keywords | tau filament / GSS / PrP-CAA / amyloid fibril / Alzheimer disease / PROTEIN FIBRIL | |||||||||
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 | helical reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
Authors | Hoq MR | |||||||||
Funding support | United States, 1 items
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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 | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_23894.map.gz | 29.4 MB | EMDB map data format | |
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Header (meta data) | emd-23894-v30.xml emd-23894.xml | 9.4 KB 9.4 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_23894_fsc.xml | 14.6 KB | Display | FSC data file |
Images | emd_23894.png | 110.4 KB | ||
Filedesc metadata | emd-23894.cif.gz | 5 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-23894 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-23894 | HTTPS FTP |
-Validation report
Summary document | emd_23894_validation.pdf.gz | 512.6 KB | Display | EMDB validaton report |
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Full document | emd_23894_full_validation.pdf.gz | 512.2 KB | Display | |
Data in XML | emd_23894_validation.xml.gz | 12.2 KB | Display | |
Data in CIF | emd_23894_validation.cif.gz | 16.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23894 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-23894 | HTTPS FTP |
-Related structure data
Related structure data | 7mkhMC 7mkfC 7mkgC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_23894.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Voxel size | X=Y=Z: 1.078 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : SF filament extracted from PrP-CAA Patient brain tissue
Entire | Name: SF filament extracted from PrP-CAA Patient brain tissue |
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Components |
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-Supramolecule #1: SF filament extracted from PrP-CAA Patient brain tissue
Supramolecule | Name: SF filament extracted from PrP-CAA Patient brain tissue type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 79 kDa/nm |
-Macromolecule #1: Isoform Tau-F of Microtubule-associated protein tau
Macromolecule | Name: Isoform Tau-F of Microtubule-associated protein tau / type: protein_or_peptide / ID: 1 / Number of copies: 10 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 45.919871 KDa |
Sequence | String: MAEPRQEFEV MEDHAGTYGL GDRKDQGGYT MHQDQEGDTD AGLKESPLQT PTEDGSEEPG SETSDAKSTP TAEDVTAPLV DEGAPGKQA AAQPHTEIPE GTTAEEAGIG DTPSLEDEAA GHVTQARMVS KSKDGTGSDD KKAKGADGKT KIATPRGAAP P GQKGQANA ...String: MAEPRQEFEV MEDHAGTYGL GDRKDQGGYT MHQDQEGDTD AGLKESPLQT PTEDGSEEPG SETSDAKSTP TAEDVTAPLV DEGAPGKQA AAQPHTEIPE GTTAEEAGIG DTPSLEDEAA GHVTQARMVS KSKDGTGSDD KKAKGADGKT KIATPRGAAP P GQKGQANA TRIPAKTPPA PKTPPSSGEP PKSGDRSGYS SPGSPGTPGS RSRTPSLPTP PTREPKKVAV VRTPPKSPSS AK SRLQTAP VPMPDLKNVK SKIGSTENLK HQPGGGKVQI INKKLDLSNV QSKCGSKDNI KHVPGGGSVQ IVYKPVDLSK VTS KCGSLG NIHHKPGGGQ VEVKSEKLDF KDRVQSKIGS LDNITHVPGG GNKKIETHKL TFRENAKAKT DHGAEIVYKS PVVS GDTSP RHLSNVSSTG SIDMVDSPQL ATLADEVSAS LAKQGL UniProtKB: Isoform Tau-F of Microtubule-associated protein tau |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | helical reconstruction |
Aggregation state | filament |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Number real images: 2004 / Average electron dose: 1.07 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |