Strain phenomenon in protein aggregation: Interplay between sequence and conformation.

Abstract

Studies of yeast and mammalian prions introduced the idea that the protein aggregates can exist in multiple stable conformations that can be propagated by seeding. These conformational states (aka strains) were shown to have distinct physical (secondary structure, stability) and biological (cytotoxicity, infectivity) properties. For mammalian prions they were also tied to differences in disease pathology and incubation time. It was later shown that this phenomenon is not limited to prion proteins, and distinct conformational states of amyloid fibrils and oligomers derived from a variety of proteins can be propagated both in vitro and in vivo. Moreover, in some cases these conformations were preserved even when propagated into a protein with a different sequence. There is now an increasing body of evidence that strain phenomenon is a generic feature of protein aggregation, and characteristic features of amyloid strains can be transmitted between unrelated sequences.