Tau destabilization in a familial deletion mutant K280 accelerates its fibrillization and enhances the seeding effect.

ABSTRACT: Tauopathies cover a range of neurodegenerative diseases in which natively unfolded tau protein aggregates and spreads in the brain during disease progression. To gain insights into the mechanism of tau structure and spreading, here, we examined the biochemical and cellular properties of human full-length wild-type and familial mutant tau, ΔK280, with a deletion at lysine 280. Our results showed that both wild-type and mutant tau are predominantly monomeric by analytical ultracentrifugation. The mutant tau may lose intramolecular contacts and is significantly destabilized assessed by cross-linking mass spectrometry and urea denaturation. Moreover, the mutant tau displayed accelerated fibril formation compared to the wild-type tau. Upon cross-seeding, the wild-type tau was seeded more easily

SUBMITTER: Chen GJ 

PROVIDER: S-EPMC11849630 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature