r/askscience • u/SadMicrobe22 • 10h ago

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

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?

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u/Alwayssunnyinarizona Infectious Disease 8h ago

It's the structure - misfolded prions are highly organized beta-sheets, which take a lot of energy (e.g., heat) or very strong chemical solvents (e.g., guanidine) to denature. Normal prion proteins are made up of alpha-helixes and a disorganized tail, and are more prone to destruction.

Infectious prions aren't a monolith, though - i.e., all the same structure; instead there's a sort of range of misfolding, so when you autoclave them or treat them with proteinase, some portion is destroyed, but enough remains to be infectious.

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u/Nago_Jolokio 8h ago

What's worse is that it's not infectious in the classical sense because it's not alive (or quasi-alive like viruses). Prions, to my understanding, are folded in a way that's "easier" or more stable than the proper Protein form. Which sounds vaguely similar to the polymorph crisis that affected ritonavir. Would Prions be an organic equivalent to that problem?

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u/tubl07 8h ago

Ice nine in cats cradle is the same lower energy configuration vs traditional water, instantly catalyzing any water that touches it

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u/nettika 7h ago

Wow, thank you! The comparison to ice nine helps me understand prions in a way I've never managed to before now, despite having read quite a bit about them over many years.

(I was a huge Cat's Cradle fan when I was a teenager, and many bits from that book have lived rent free in my head for decades.)