Hello! I'm desperately trying to find clues to the molecular mechanism of prion replication: how do misfolded (scrapie form) PrPs actually catalyze misfolding of the normal cellular PrPs on molecular/biochemical level? I understand that it is not completely cleared out, but I couldn't find any molecular/biochemical hypotheses. Everyone seems to just skip this issue in any paper I could get my hands in the past few days. Also, what is the biochemical reasons for which such saturation with beta-sheets renders PrPsc protease-resistant? Isn't there really any proteases specific enough to degrade high beta-sheet-content proteins? Or does it have to do with relatively rapid formation of amyloid fibers? Or does it have to do with chaperon malfunction (thus potentially mutation in chaperon genes as well)?
Thanks!