Elucidation of the Aggregation Pathways of Helix-Turn-Helix Peptides: Stabilization at the Turn Region Is Critical for Fibril Formation.

ABSTRACT: Aggregation of proteins to fiberlike aggregates often involves a transformation of native monomers to β-sheet-rich oligomers. This general observation underestimates the importance of α-helical segments in the aggregation cascade. Here, using a combination of experimental techniques and accelerated molecular dynamics simulations, we investigate the aggregation of a 43-residue, apolipoprotein A-I mimetic peptide and its E21Q and D26N mutants. Our study indicates a strong propensity of helical segments not to adopt cross-β-fibrils. The helix-turn-helix monomeric conformation of the peptides is preserved in the mature fibrils. Furthermore, we reveal opposite effects of mutations on and near the turn region in the self-assembly of these peptides. We show that the E21-R24 salt bridge is a major

SUBMITTER: Do TD 

PROVIDER: S-EPMC4526104 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature