Heterogeneous seeding of HET-s(218-289) and the mutability of prion structures

Abstract

One fundamental property of prions is the formation of strains-prions that have distinct biological effects, despite a common amino acid sequence. The strain phenomenon is thought to be caused by the formation of different molecular structures, each encoding for a particular biological activity. Whilethe precise mechanism of the formationof strains isunknown, they tend to arise following environmental changes, such as passage between different species. One possible mechanism discussed here is heterogeneous seeding; the formation of a prion nucleated by a differentmolecular structure. While heterogeneous seeding is not the only mechanism of prion mutation, it is consistent with some observations on species adaptation and drug resistance. Heterogeneous seeding provides a useful framework to understand how prions can adapt to new environmental conditions and change biological phenotypes.