Solid-state NMR reveals a comprehensive view of the dynamics of the flexible, disordered N-terminal domain of amyloid-β fibrils.

ABSTRACT: Amyloid fibril deposits observed in Alzheimer's disease comprise amyloid-β (Aβ) protein possessing a structured hydrophobic core and a disordered N-terminal domain (residues 1-16). The internal flexibility of the disordered domain is likely essential for Aβ aggregation. Here, we used ²H static solid-state NMR methods to probe the dynamics of selected side chains of the N-terminal domain of Aβ_1-40 fibrils. Line shape and relaxation data suggested a two-state model in which the domain's free state undergoes a diffusive motion that is quenched in the bound state, likely because of transient interactions with the structured C-terminal domain. At 37 °C, we observed freezing of the dynamics progressively along the Aβ sequence, with the fraction of the bound state increasing

SUBMITTER: Au DF 

PROVIDER: S-EPMC6463690 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature