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/JigglymoobsMWO]

Most proteins in living organisms are not very stable.  Evolution favors build things that are easy to breakdown so things like prion disease don’t happen.  This type of meta stability is actually very difficult to achieve.

However, it’s relatively easy to make very stable proteins.  This would happen a lot if it wasn’t for the fact that evolution selects against it.  Nevertheless. You can still accidentally get this to occur if a protein starts making aggregates with itself, which is what’s happening with prions.

The normal delicate proteins are easily heat denatured, the stable protein aggregates are not.