The Lys 280 → Gln mutation mimicking disease-linked acetylation of Lys 280 in tau extends the structural core of fibrils and modulates their catalytic properties.

ABSTRACT: Amyloid fibrillar aggregates isolated from the brains of patients with neurodegenerative diseases invariably have post-translational modifications (PTMs). The roles that PTMs play in modulating the structures and polymorphism of amyloid aggregates, and hence their ability to catalyze the conversion of monomeric protein to their fibrillar structure is, however, poorly understood. This is particularly true in the case of tau aggregates, where specific folds of fibrillar tau have been implicated in specific tauopathies. Several PTMs, including acetylation at Lys 280, increase aggregation of tau in the brain, and increase neurodegeneration. In this study, tau-K18 K280Q, in which the Lys 280 → Gln mutation is used to mimic acetylation at Lys 280, is shown, using HX-MS measurements, to form fibr

SUBMITTER: Kumar H 

PROVIDER: S-EPMC7980515 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature