Albumin Alters the Conformational Ensemble of Amyloid-β by Promiscuous Interactions: Implications for Amyloid Inhibition.

ABSTRACT: Human serum albumin (HSA) is a key endogenous inhibitor of amyloid-β (Αβ) aggregation. In vitro HSA inhibits Aβ fibrillization and targets multiple species along the aggregation pathway including monomers, oligomers, and protofibrils. Amyloid inhibition by HSA has both pathological implications and therapeutic potential, but the underlying molecular mechanism remains elusive. As a first step towards addressing this complex question, we studied the interactions of an Aβ42 monomer with HSA by molecular dynamics simulations. To adequately sample the conformational space, we adapted the replica exchange with solute tempering (REST2) method to selectively heat the Aβ42 peptide in the absence and presence of HSA. Aβ42 binds to multiple sites on HSA with a preference to domain III and adopts vari

SUBMITTER: Xie H 

PROVIDER: S-EPMC7940760 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature