Direct Observation of Competing Prion Protein Fibril Populations with Distinct Structures and Kinetics.

ABSTRACT: In prion diseases, fibrillar assemblies of misfolded prion protein (PrP) self-propagate by incorporating PrP monomers. These assemblies can evolve to adapt to changing environments and hosts, but the mechanism of prion evolution is poorly understood. We show that PrP fibrils exist as a population of competing conformers, which are selectively amplified under different conditions and can "mutate" during elongation. Prion replication therefore possesses the steps necessary for molecular evolution analogous to the quasispecies concept of genetic organisms. We monitored structure and growth of single PrP fibrils by total internal reflection and transient amyloid binding super-resolution microscopy and detected at least two main fibril populations, which emerged from seemingly homogeneous PrP s

SUBMITTER: Sun Y 

PROVIDER: S-EPMC10100569 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature