Abstract
The great progress made in defining the structure of protein and peptide amyloid assemblies, particularly the arrangement of peptides in β-sheets, is counterbalanced by the still poor understanding of the higher organization of β-sheets within the fibril and overall fibril/fibril associations. The assembly pathway and basis of amyloid toxicity may well depend on these higher-order structural features. For example, significant evidence points to association between sheets as the rate limiting step in fibril assembly, and a critical metal binding site has now been identified that involves residues from different individual sheets. Here we review experiments that are identifying some of the issues associated with sheet–sheet association by investigating simple model peptides derived from the central core of the Aβ peptide implicated in Alzheimer's disease. These peptides transit between fibril/ribbon/nanotube morphologies in response to assembly conditions, laying the foundation for understanding the folding landscape for these higher order assemblies, revealing potential targets for therapeutic intervention, and opening strategies for the design of highly ordered peptide self-assembled microscale morphologies.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call