The normally shaped proteins are produced routinely as part of the organism's normal function. I believe that what happens is that the misfolded prion interacts with the normally folded protein and causes it to refold in an abnormal manner. The newly abnormally folded protein then goes on to induce other normally folded proteins to change to a misfolded conformation. It has an exponential effect.
Why is PrP so structurally sound and resistant to protease enzyme destruction? Heat at 600 degree C., Boiling water, radiation .... Wow..
There are a couple of possibilities that might make prions resistant to degradation by proteases. One would be that the ubiquitination sites contained in all proteins are masked when the prion is misfolded. Ubiquitin is a small protein that recognizes and attaches to a specific amino acid sequence in a protein. That ubiquitin tag tells the protein to go to the proteasome, where it is degraded. Normally, ubiquitin recognizes and tags misfolded proteins.
The other possibility is that the prions are ubiquitinated normally, but the protease binding sites are masked, so the proteases cannot cleave the prions.
Without doing more reading, I cannot say if either or both of those mechanisms are protecting prions from degradation. But those are my educated guesses as to what may be going on.
As for prions being resistant to other processes that often destroy proteins--not all proteins are susceptible to all denaturing processes. It is actually not uncommon for proteins to survive boiling, for example. It's just that prions incorporate more features rendering them resistant to destruction than we observe in the vast majority of proteins.
Thank you for taking the time to answer my questions. As usual, answers lead to more questions! I’ll be doing some reading and research to take it further. Two of my children are performing cloning and genetic engineering in medical schools, but they no longer live at home. I miss having them here to answer my questions.