Phosphorylation of Tau R2 Repeat Destabilizes Its Binding to Microtubules: A Molecular Dynamics Simulation Study.

ABSTRACT: Phosphorylation, the most popular post-translational modification of tau protein, plays an important role in regulating tau physiological functions. However, aberrant phosphorylation attenuates the binding affinity of tau to a microtubule (MT), resulting in MT destabilization followed by accumulation of neurofibrillary tangles in the brain. There are in total 85 potential phosphorylation sites in a full-length tau protein, and about half of them are abnormal as they occur in tau of Alzheimer's disease (AD) brain only. In this work, we investigated the impact of abnormal Ser289, Ser293, and Ser289/Ser293 phosphorylation on tau R2-MT binding and the conformation of tau R2 using molecular dynamics simulation. We found that the phosphorylation significantly affected R2-MT interaction and reduc

SUBMITTER: Man VH 

PROVIDER: S-EPMC10032563 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature