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

ABSTRACT: 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 understood. 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 re

SUBMITTER: Igel-Egalon A 

PROVIDER: S-EPMC6778151 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature