Post-Translational Modifications Control Phase Transitions of Tau.

ABSTRACT: The self-assembly of Tau into filaments, which mirror the structures observed in Alzheimer's disease (AD) brains, raises questions about the role of AD-specific post-translational modifications (PTMs) in the formation of paired helical filaments (PHFs). To investigate this, we developed a synthetic approach to produce Tau(291-391) featuring N-acetyllysine, phosphoserine, phosphotyrosine, and N-glycosylation at positions commonly modified in post-mortem AD brains. Using various electron and optical microscopy techniques, we discovered that these modifications generally hinder the in vitro assembly of Tau into PHFs. Interestingly, while acetylation's effect on Tau assembly displayed variability, either promoting or inhibiting phase transitions in cofactor-free aggregatio

SUBMITTER: Powell WC 

PROVIDER: S-EPMC11613296 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature