Misfolding and Self-Assembly Dynamics of Microtubule-Binding Repeats of the Alzheimer-Related Protein Tau.

ABSTRACT: Pathological aggregation of intrinsically disordered tau protein, driven by the interactions between microtubule-binding (MTB) domains, is associated with Alzheimer's disease. The MTB domain contains either three or four repeats with sequence similarities. Compared to amyloid β, many aspects of the misfolding and aggregation mechanisms of tau are largely unknown. In this study, we systematically investigated the dynamics of monomer misfolding and dimerization of each MTB repeat using atomistic discrete molecular dynamic simulations. Our results revealed that all the four repeat monomers (R1-R4) were very dynamic, featuring frequent conformational conversion and lacking stable conformations. While R1, R2, and R4 monomers occasionally adopted partially helical conformations, R3 monomers freq

SUBMITTER: He H 

PROVIDER: S-EPMC8238895 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature