Mutations Alter RNA-Mediated Conversion of Human Prions

Prion diseases are connected with self-replication and self-propagation of misfolded proteins. The rate-limiting factor is the formation of the initial seed. We have recently studied the early stages in the conversion between functional PrPC and the infectious scrapie PrPSC form, triggered by the binding of RNA. Here, we study how this process is modulated by the prion sequence. We focus on residues 129 and 178, which are connected to the hereditary neurodegenerative disease fatal familial insomnia.