Cross-Seeding with Homologous Sequences Alters Amyloid Aggregation Kinetics and Fibril Structure.

Abstract

Protein aggregation through homotypic interactions is a hallmark of neurodegenerative diseases. Recently, heterotypic amyloid interactions through cross-seeding were found to modify protein aggregation and are reported in the brain of Alzheimer's disease patients. However, whether amyloid-β (Aβ) assembly can be modulated by heterotypic interactions between Aβ aggregation-prone regions (APRs) and short homologous segments in unrelated human proteins needs to be elucidated. A recent study revealed that the aggregation kinetics and fibril morphology of Aβ is altered by heterotypic interactions between its APRs and homologous segments of unrelated proteins. The data provide novel insights into the structure, origins, and aggregation principles of the amyloid assembly process.