Amyloid fibrils are self-associating filamentous structures formed from the 39- to 42-residue-long amyloid β peptide (Aβ peptide). The deposition of Aβ fibrils is one of the most important factors in the pathogenesis of Alzheimer's disease. Aβ25-35 is a fibril-forming peptide that is thought to represent the biologically active, toxic form of the full-length Aβ peptide. We have recently shown that β sheets can be mechanically unzipped from the fibril surface with constant forces in a reversible transition, and the unzipping forces differ in fibrils composed of different peptides. In the present work, we explored the effect of ε-amino acetylation of the Lys28 residue on the magnitude of the unzipping force of Aβ25-35 fibrils. Although the gross structure of the Lys28-acetylated (Aβ25-35_K28Ac) and wild-type Aβ25-35 (Aβ25-35wt) fibrils were similar, as revealed by atomic force microscopy, the fundamental unzipping forces were significantly lower for Aβ25-35_K28Ac (20±4 pN SD) than for Aβ25-35wt (42±9 pN SD). Simulations based on a simple two-state model suggest that the decreased unzipping forces, caused most likely by steric constraints, are likely due to a destabilized zippered state of the fibril.
ASJC Scopus subject areas
- Chemical Engineering(all)
- Computer Science Applications
- Library and Information Sciences