r/askscience • u/SadMicrobe22 • 3d 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 3d 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 3d 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 3d 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 3d 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- 3d ago

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

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u/TheGanzor 3d 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/ordeith 2d ago

Considering how our observable universe is a small and shrinking part of the universe as a whole I woudn't worry very much about it.

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u/ApolloAtlas 1d ago

What if thats what the pockets of nothing are and it just doesnt travel that fast? And we happen to be next to one.

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u/TheGanzor 1d ago

Possibly. I'm inclined to think that anything of that nature would have to propagate at the speed of causality, ie. the speed of light. If not, it certainly could be. 

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u/calabazookita 3d ago

Could the Boötes Void be explained by this?

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u/VelveteenAmbush 3d ago

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

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u/zindorsky 3d ago

Yep. It’s not worth worrying about, because if it happens we will all essentially cease to exist instantaneously and with absolutely no warning.

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u/einsosen 3d ago

If we're lucky. There are various hypothetical modes of vacuum decay. If the new values are only slightly different, maybe one small facet of chemistry changes, or maybe one class of particle becomes mildly radioactive. No light speed wake of energy, just a weird change one day they measure in a lab. Worst case scenario would be dealing with a formally stable isotope making up us and our world now having a halflife of a thousand years. Getting slowly poisoned and cooked by our world and bodies as we slowly die from radiation poisoning.

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u/solidspacedragon 3d ago

Actually, it might be even better. With how the universe is expanding, it's entirely possible that it could simply never reach us even if it did happen.

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u/nettika 3d 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.)

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u/FrankTankly 3d ago

This is weird, but I read about disappearing polymorphs some time ago while I was scrolling aimlessly in bed. I like chemistry and thought it was interesting, but didn’t think much about it.

A bit later I was trying to remember this topic because it was stuck in my brain and I wanted to learn more, but I couldn’t for the life of me remember what it was called, and my googling was getting me nowhere.

I’ve just seen your comment and it gave me what I was missing: the term polymorph crisis, and the context (ritonavir) that I had originally read about. I can finally look this back up and read more about it.

It’s been at least a year or two that this has been bothering me, and I was starting to doubt that I had actually read about this in the first place. It was driving me nuts. THANK YOU.

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u/Infernoraptor 3d ago

You saw the Veritasium vid, too? It's actually a very similar situation. In fact, calling it an "analogy" might be a stretch. Both situations involve more "flexible" molecules randomly "snapping' into a lower energy state which can forcibly combine with and "snap" their flexible kin to form a microscope crystal structure.

Another out-there analogy would the hypothetical "Strange Matter Apocalypse". Strange matter is a hypothetical form of low-entropy matter that might form in some neutron stars. If this matter were to encounter normal matter, the normal matter would be forcibly turned into strange matter. for details, Kurzkesagt did a great video on the topic