Edge Strand Dissociation and Conformational Changes in Transthyretin under Amyloidogenic Conditions.

ABSTRACT: During amyloidogenesis, proteins undergo conformational changes that allow them to aggregate and assemble into insoluble, fibrillar structures. Soluble oligomers that form during this process typically contain 2-24 monomeric subunits and are cytotoxic. Before the formation of these soluble oligomers, monomeric species first adopt aggregation-competent conformations. Knowledge of the structures of these intermediate states is invaluable to the development of molecular strategies to arrest pathological amyloid aggregation. However, the highly dynamic and interconverting nature of amyloidogenic species limits biophysical characterization of their structures during amyloidogenesis. Here, we use molecular dynamics simulations to probe conformations sampled by monomeric transthyretin under amylo

SUBMITTER: Childers MC 

PROVIDER: S-EPMC7732750 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature