Thank you for posting. This is excellent research. One step closer to understanding prions.
Questions from a novice:
“What causes the proteins to fold, replicate and become prions if there is no DNA, or RNA?” Another enzyme?
“Why is PrP so structurally sound and resistant to protease enzyme destruction?” Heat at 600 degree C., Boiling water, radiation .... Wow..
I find the research this past year showing how the lichen Parmelia sulcata when consumed by deer, elk and moose denature the prions in chronic wasting disease in the wild. Is is possible that the solution to denaturing prions is with fungal prions that do not affect humans? If PrPc is necessary for long term potentiation in the hippocampus and the variations of PrPsc block potentiation by creating amyloid plaques, the firewall to block Alzheimer’s just might be found in lichen prion research.
Natural Born Prion Killers: Lichens Degrade “Mad Cow” Related Brain Pathogen
By Philip Yam | May 19, 2011
http://blogs.scientificamerican.com/observations/2011/05/19/natural-born-prion-killers-lichens-degrade-mad-cow-related-brain-pathogen/?print=true
Too bad I’m over the hill. I would love to return to the university for a degree in microbiology/biochemistry. This stuff sure beats crossword puzzles! I find the whole field of epigenetic research and all of its sub fields absolutely fascinating.
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.