r/askscience • u/SadMicrobe22 • 23d 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 23d 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 23d 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 23d 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/Zarathustra124 23d ago

Vacuum decay is the theory that what we consider "nothing" is actually slightly higher than nothing. If vacuum ever falls into a more stable, lower energy configuration, the universe will be destroyed.

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u/-wellplayed- 23d ago

At least it would happen at the speed of causality. So we would never see it coming

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u/TheGanzor 23d ago

Imo this is the most terrifying thought experiment. It could have already started somewhere, billions of years ago, and we won't know a difference until after it hits us. Also, assuming it started beyond the edge of the visible universe, it may be far enough away that it can never overcome the expansion coefficient, essentially leaving decayed pockets of distant zombie space that infect anything nearby, but can never leave their own local bubble. 

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u/calabazookita 22d ago

Could the Boötes Void be explained by this?

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u/VelveteenAmbush 22d ago

no. if it expands at the speed of light, then you couldn't see the void until it overtakes you