Direct Observation of Murine Prion Protein Replication in Vitro.

ABSTRACT: Prions are believed to propagate when an assembly of prion protein (PrP) enters a cell and replicates to produce two or more fibrils, leading to an exponential increase in PrP aggregate number with time. However, the molecular basis of this process has not yet been established in detail. Here, we use single-aggregate imaging to study fibril fragmentation and elongation of individual murine PrP aggregates from seeded aggregation in vitro. We found that PrP elongation occurs via a structural conversion from a PK-sensitive to PK-resistant conformer. Fibril fragmentation was found to be length-dependent and resulted in the formation of PK-sensitive fragments. Measurement of the rate constants for these processes also allowed us to predict a simple spreading model for aggregate propagation thro

SUBMITTER: Sang JC 

PROVIDER: S-EPMC6225343 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature