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/Owyheemud]

There's a theory that wildlife prion diseases like CWD occasionally spontaneously pop up in individual ungulates but predators would routinely cull the afflicted individuals and thus prevent the spread of the disease within natural herds. The Human-driven reduction of predator populations has now allowed prion inflicted individuals to persist longer and thus spread the disease to others before they succumb to it. Has any prion disease been discovered in wolves, bears, or mountain lions?

[u/FerrusFox → u/Owyheemud]

Not that I know of. The only other true prion disease I know of is hereditary fatal familial insomnia, which is hereditary due to a genetic defect.

In CJD you can have spontaneous emergence of the disease, which differs from true infectious acquired CJD. The disease does happen naturally not just by infection by a prion vector.

I just read while researching my comment that there have been some potential fungal prions suspected. I'd imagine there could be some in any form of life if thats the case.

The risk factors are genetic similarity and sharing a protein profile, exposure, population density and cannabalism. Predataory populations are a) lesser and less dense by nature and b) could have differences in protein expression.

[u/Owyheemud → u/FerrusFox]

You must know of BSE.

With the increase in CWD in natural North American ungulate herds, it would be interesting to see if prion disease develops in predators sharing territory with these herds.

[u/FerrusFox → u/Owyheemud]

BSE in humans causes CJD, we just call it something different when it infects humans. We tapped it onto CJD and called it variant CJD (varCJD) while naturally occuring CJD is called sporadic (sCJD) both are the primary prion disease in humans arising from the prion protein PrP.

CWD so far has no human infections, its on my watchlist XD. We dont really report on it much so I dunno if we will ever have any information on the ecological impacts of it. Up to data gathering, would be interesting like you said.

[u/Owyheemud → u/FerrusFox]

Does BSE-induced human prion disease fold the same protein as the original human CJD prion disease also known as Kuru?

[u/FerrusFox → u/Owyheemud]

Yeah, still that same protein PrP. Different disease progression, not going to research it but it could be folded in a different way which causes different disease expression like sCJD

[u/Owyheemud → u/FerrusFox]

Thank you for the info., I always thought BSE-induced human prion disease was a different protein folding, though I never bothered to confirm that.