⮝ Full datasets listing

PXD025663

PXD025663 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleStructure of Tau filaments in Prion protein amyloidoses
DescriptionIn 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) and Gerstmann-Sträussler-Scheinker (GSS) disease, two genetically determined Prion protein (PrP) amyloidoses characterized by the deposition of PrP amyloid (APrP) in the vessel walls and in the cerebral parenchyma, respectively. A nonsense and a missense mutation in the PRNP gene lead to a premature termination of translation at codon position 160 (Q160Ter) of PrP in PrP-CAA, or to the substitution of an amino acid at residue 198 (F198S) of PrP in GSS. These two diseases have different clinical and pathologic phenotypes; however, in both diseases, neuropathologic analyses 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 and GSS are composed of 3-repeat and 4-repeat Tau isoforms, having a striking similarity to NFTs in Alzheimer disease (AD). In PrP-CAA, Tau filaments are made of both paired helical filaments (PHFs) and straight filaments (SFs), while in GSS only PHFs were found. Mass spectrometry analyses of Tau filaments extracted from PrP-CAA and GSS 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 and GSS 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 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.
HostingRepositoryPRIDE
AnnounceDate2022-02-17
AnnouncementXMLSubmission_2022-02-17_03:02:20.281.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD025663
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterEmma Doud
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListubiquitinylated lysine; phosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-04-27 08:33:51ID requested
12022-02-17 03:02:21announced
Publication List
Hallinan GI, Hoq MR, Ghosh M, Vago FS, Fernandez A, Garringer HJ, Vidal R, Jiang W, Ghetti B, Structure of Tau filaments in Prion protein amyloidoses. Acta Neuropathol, 142(2):227-241(2021) [pubmed]
Keyword List
submitter keyword: Brain, GSS, PrP-CAA, Tau, APrP, Cryo-EM, seeding, neurodegeneration
Contact List
Ruben Vidal
contact affiliationDept. of Pathology and Laboratory Medicine, Indiana University School of Medicine, 635 Barnhill Dr., MSB A136, Indianapolis, IN 46202
contact emailrvidal@iupui.edu
lab head
Emma Doud
contact affiliationIndiana University School of Medicine
contact emailedoud@iu.edu
dataset submitter
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/02/PXD025663
PRIDE project URI
Repository Record List
[ + ]