Molecular insights into the surface-catalyzed secondary nucleation of amyloid-β₄₀ (Aβ₄₀) by the peptide fragment Aβ_16-22.

ABSTRACT: Understanding the structural mechanism by which proteins and peptides aggregate is crucial, given the role of fibrillar aggregates in debilitating amyloid diseases and bioinspired materials. Yet, this is a major challenge as the assembly involves multiple heterogeneous and transient intermediates. Here, we analyze the co-aggregation of Aβ₄₀ and Aβ_16-22, two widely studied peptide fragments of Aβ₄₂ implicated in Alzheimer's disease. We demonstrate that Aβ_16-22 increases the aggregation rate of Aβ₄₀ through a surface-catalyzed secondary nucleation mechanism. Discontinuous molecular dynamics simulations allowed aggregation to be tracked from the initial random coil monomer to the catalysis of nucleation on the fibril surface. Together, th

SUBMITTER: Bunce SJ 

PROVIDER: S-EPMC6588359 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature