Frustrated peptide chains at the fibril tip control the kinetics of growth of amyloid-β fibrils.

ABSTRACT: Amyloid fibrillization is an exceedingly complex process in which incoming peptide chains bind to the fibril while concertedly folding. The coupling between folding and binding is not fully understood. We explore the molecular pathways of association of Aβ40 monomers to fibril tips by combining time-resolved in situ scanning probe microscopy with molecular modeling. The comparison between experimental and simulation results shows that a complex supported by nonnative contacts is present in the equilibrium structure of the fibril tip and impedes fibril growth in a supersaturated solution. The unraveling of this frustrated state determines the rate of fibril growth. The kinetics of growth of freshly cut fibrils, in which the bulk fibril structure persists at the tip, complemented by molecula

SUBMITTER: Xu Y 

PROVIDER: S-EPMC8463807 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature