Co-factor-free aggregation of tau into seeding-competent RNA-sequestering amyloid fibrils.

ABSTRACT: Pathological aggregation of the protein tau into insoluble aggregates is a hallmark of neurodegenerative diseases. The emergence of disease-specific tau aggregate structures termed tau strains, however, remains elusive. Here we show that full-length tau protein can be aggregated in the absence of co-factors into seeding-competent amyloid fibrils that sequester RNA. Using a combination of solid-state NMR spectroscopy and biochemical experiments we demonstrate that the co-factor-free amyloid fibrils of tau have a rigid core that is similar in size and location to the rigid core of tau fibrils purified from the brain of patients with corticobasal degeneration. In addition, we demonstrate that the N-terminal 30 residues of tau are immobilized during fibril formation, in agreement with the pres

SUBMITTER: Chakraborty P 

PROVIDER: S-EPMC8270918 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature