Impact of the Hereditary P301L Mutation on the Correlated Conformational Dynamics of Human Tau Protein Revealed by the Paramagnetic Relaxation Enhancement NMR Experiments.

ABSTRACT: Tau forms intracellular insoluble aggregates as a neuropathological hallmark of Alzheimer's disease. Tau is largely unstructured, which complicates the characterization of the tau aggregation process. Recent studies have demonstrated that tau samples two distinct conformational ensembles, each of which contains the soluble and aggregation-prone states of tau. A shift to populate the aggregation-prone ensemble may promote tau fibrillization. However, the mechanism of this ensemble transition remains elusive. In this study, we explored the conformational dynamics of a tau fragment by using paramagnetic relaxation enhancement (PRE) and interference (PRI) NMR experiments. The PRE correlation map showed that tau is composed of segments consisting of residues in correlated motions. Intriguingly,

SUBMITTER: Kawasaki R 

PROVIDER: S-EPMC7313075 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature