PXD016862

PXD016862 is an original dataset announced via ProteomeXchange.

Title	Posttranslational modifications mediate the structural diversity of tauopathy strains
Description	Tau aggregation is the defining pathological hallmark of tauopathies, but structural insights are revealing key differences between filaments across this class of disorders. Using cryo-electron microscopy, we identify a 107-residue fragment, K274-E380, which forms the insoluble core of tau filaments in the tauopathy corticobasal degeneration (CBD). This tau conformer is distinct from those identified in Alzheimer’s Disease (AD), Pick’s Disease, and Chronic Traumatic Encephalopathy, pointing towards a “one strain per disease” paradigm. Each disease-specific conformer can pack into multiple fibril subtypes and, despite similarities in secondary structure elements between tau filaments from CBD and AD, mass spectrometry revealed key differences in posttranslational modifications (PTMs). Given the abundance of lysine residues in the insoluble tau filament core in both CBD and AD, ubiquitination and acetylation are identified as key PTMs that compete to modify specific residues, which may ultimately determine filament morphology.
HostingRepository	PRIDE
AnnounceDate	2020-02-14
AnnouncementXML	Submission_2020-02-14_10:29:47.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Duc Duong
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitinylated lysine; methylated residue; phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2019-12-20 02:25:34	ID requested
⏵ 1	2020-02-14 10:29:49	announced

Arakhamia T, Lee CE, Carlomagno Y, Duong DM, Kundinger SR, Wang K, Williams D, DeTure M, Dickson DW, Cook CN, Seyfried NT, Petrucelli L, Fitzpatrick AWP, Posttranslational Modifications Mediate the Structural Diversity of Tauopathy Strains. Cell, 180(4):633-644.e12(2020) [pubmed]

submitter keyword: CBD, TAU, Mass spectrometry

Nicholas Seyfried
contact affiliation	Emory University
contact email	nseyfri@emory.edu
lab head
Duc Duong
contact affiliation	Center of Neurodegenerative Diseases
contact email	dduong@emory.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD016862
     1. Label: PRIDE project
     2. Name: Posttranslational modifications mediate the structural diversity of tauopathy strains