Data from: Early stage prion assembly involves two subpopulations with different quaternary structures and a secondary templating pathway

The dynamics of aggregation and structural diversification of misfolded,
host-encoded proteins in neurodegenerative diseases are poorly understood.
In many of these disorders, including Alzheimer’s, Parkinson’s and prion
diseases, the misfolded proteins are self-organized into conformationally
distinct assemblies or strains. The existence of intrastrain structural
heterogeneity is increasingly recognized. However, the underlying
processes of emergence and coevolution of structurally distinct assemblies
are not mechanistically supported. Here, we show that early prion
replication generates two subsets of structurally different assemblies by
two sequential processes of formation, regardless of the strain
considered. The first process corresponds to a quaternary structural
convergence, by reducing the parental strain polydispersity to generate
small oligomers. The second process transforms these oligomers into larger
ones, by a secondary autocatalytic templating pathway requiring the prion
protein. This pathway provides first mechanistic insights into prion
structural diversification, a key determinant for prion adaptation and
toxicity.