Cofactor molecules maintain infectious conformation and restrict strain properties in purified prions

摘要

Mammalian prions are unorthodox infectious agents that cause fatal neurological diseases such as Creutzfeldt-Jakob disease, bovine spongiform encephalopathy (also known as "mad cow disease"),and scrapie. Prions lack informational nucleic acids; therefore, it is puzzling that they replicate within and cause specific patterns of disease in infected hosts. Prions are formed by the conversion of a normal cellular prion protein (PrP~c) into a misfolded shape called the "scrapie prion protein" (PrP~(Sc)). According to the popular "protein only" hypothesis, PrP~(Sc) may be the only essential component of the infectious agent, possessing the ability to replicate and cause disease by inducing the conversion of PrP~c molecules into additional PrP~(Sc) molecules. Here, we demonstrate that cofactor molecules appear to be necessary to maintain PrP~(Sc) structure and that specific sets of cofactor molecules may generate specific prion strains (Fig. PI).