Induced Dipole-Dipole Interactions Influence the Unfolding Pathways of Wild-Type and Mutant Amyloid β-Peptides.

ABSTRACT: Amyloid-forming proteins undergo a structural transition from α-helical to disordered conformations and, ultimately, cross-β fibrils. The unfolding and aggregation of the amyloid β-peptide (Aβ) have been implicated in the development and progression of Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). However, the events underlying the initial structural transition leading to the disease state remain unclear. Although most cases are sporadic, several genetic variants exist that alter the electrostatic properties of Aβ and lead to more rapid unfolding and more severe phenotypes. In the present study, the enhanced unfolding is shown to be due to the mutated side chains altering the local peptide-bond dipole moments leading to local destabilization of the α-helix, as determined

SUBMITTER: Lemkul JA 

PROVIDER: S-EPMC4690986 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature