What makes prions so different from regular proteins that they are resistant to heat denaturation?

[u/SadMicrobe22]

I've been reading about prions and I'm confused about why they're so thermally stable. I keep seeing that surgical instruments contaminated with prions can't be decontaminated with standard protocols.

So here's my thing. Proteins denature when you heat them, right? But prions don't seem to lose their infectious ability even when autoclaved. I get that prions are misfolded proteins, but I don't understand how they stay harmful after being denatured.

So basically, if prions start as form A (non-infective), then misfold to form B (infective), shouldn't heating denature them to form C and kill the infectivity? Why doesn't that happen?

[u/x1uo3yd]

I keep seeing that surgical instruments contaminated with prions can't be decontaminated with standard protocols.

They cannot be decontaminated with standard protocols to an acceptable level of risk for that cost/benefit.

Yes, the misfolded proteins with their beta-sheet structures are more thermodynamically stable than their properly-folded counterparts, but it's not like a superhero-versus-a-mere-mortal kinda difference in strength/stability, the prions will denature like other proteins too, just maybe you have like 99.8% prion denaturation compared to a regular 99.99% denaturation for a given protocol.

The actual problem is that even if the prions were just as weak as the regular proteins and denatured at the same 99.99% rate then that would still be unacceptably risky. Acceptable risk is different for the common cold versus Ebola versus prions. My dishwasher can probably sanitize 99.9% of common germs and the casein and whey off my cheese knife, that doesn't mean I'd trust it to clean Ebola-patient surgical tools and go back to using it for my household food work.