Early Stages of RNA-Mediated Conversion of Human Prions

Prion diseases are characterized by the conversion of prion proteins from a PrPC fold into a disease-causing PrPSC form that is self-replicating. A possible agent to trigger this conversion is polyadenosine RNA, but both mechanism and pathways of the conversion are poorly understood. Using coarse-grained molecular dynamic simulations we study the time evolution of PrPC over 600 mu s. We find that both the D178N mutation and interacting with polyadenosine RNA reduce the helicity of the protein and encourage formation of segments with strand-like motifs. We conjecture that these transient ss-strands nucleate the conversion of the protein to the scrapie conformation PrPSC.

Automated summary

This study utilizes molecular dynamic simulations to investigate the time evolution of PrPC in the presence of D178N mutation and polyadenosine RNA. The findings suggest that both factors reduce the helical structure of the protein and promote the formation of strand-like motifs, potentially initiating the conversion of PrPC to the PrPSC scrapie conformation.