Tau local structure shields an amyloid-forming motif and controls aggregation propensity.

ABSTRACT: Tauopathies are neurodegenerative diseases characterized by intracellular amyloid deposits of tau protein. Missense mutations in the tau gene (MAPT) correlate with aggregation propensity and cause dominantly inherited tauopathies, but their biophysical mechanism driving amyloid formation is poorly understood. Many disease-associated mutations localize within tau's repeat domain at inter-repeat interfaces proximal to amyloidogenic sequences, such as ³⁰⁶VQIVYK³¹¹. We use cross-linking mass spectrometry, recombinant protein and synthetic peptide systems, in silico modeling, and cell models to conclude that the aggregation-prone ³⁰⁶VQIVYK³¹¹ motif forms metastable compact structures with its upstream sequence that modulates aggregation propensity. We

SUBMITTER: Chen D 

PROVIDER: S-EPMC6555816 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature