PXD062343-2

PXD062343 is an original dataset announced via ProteomeXchange.

Title	Seed structure and phosphorylation in the fuzzy coat impact tau seeding competency
Description	Tau is a pathogenic protein in Alzheimer’s (AD) and other neurodegenerative diseases. The misfolding of tau into β-sheet rich elongated filaments is thought to be a key event in disease pathogenesis, followed by subsequent templated recruitment of monomeric tau into this pathogenic form. Cryo-electron microscopy has revealed that specific tau conformations characterize different diseases. In this study, we explored how tau filament core structure and post-translational modifications in its disordered fuzzy coat influence its seeding capacity in primary neurons and mice. We show that the structure of the seeds affects seeding capacity, but that the AD tau core structure alone is insufficient to capture the full seeding capacity of AD tau. Proteolytic cleavage of AD tau which removes the fuzzy coat causes a loss in seeding capacity, as does removal of phosphorylation from the fuzzy coat by phosphatase treatment. Re-phosphorylation of phosphatase-treated AD tau by kinase treatment partially restores seeding activity. Finally, we find that filaments of recombinant tau with twelve phospho-mimetic residues (PAD12 tau) with the AD fold are able to recapitulate the seeding capacity of AD tau. Combined, these results suggest that the structure of the ordered core, together with phosphorylation in the fuzzy coat, confers the seeding capacity of tau filaments.
HostingRepository	PRIDE
AnnounceDate	2025-08-11
AnnouncementXML	Submission_2025-08-11_15:09:11.021.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hyoungjoo Lee
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-28 05:29:39	ID requested
1	2025-08-05 02:05:52	announced
⏵ 2	2025-08-11 15:09:11	announced	2025-08-11: Updated project metadata.

10.1101/2025.03.07.642026.;

submitter keyword: tauopathy,seeding, phosphorylation, prion-like, 4R, 3R

Michael X. Henderson
contact affiliation	1Department of Neurodegenerative Science, Van Andel Institute
contact email	michael.henderson@vai.org
lab head
Hyoungjoo Lee
contact affiliation	Van Andel Institute
contact email	hyoungjoo.lee@vai.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD062343
     1. Label: PRIDE project
     2. Name: Seed structure and phosphorylation in the fuzzy coat impact tau seeding competency