5 ms·

Yeah, I'm not an expert but I've heard experts discuss it as though they're almost impossible to sterilize. As a layman, I imagine this has something to do wit

Yeah, I'm not an expert but I've heard experts discuss it as though they're almost impossible to sterilize. As a layman, I imagine this has something to do with the fact that your task is essentially to break down a molecule (a protein) instead of a structure of molecules (a virus or bacteria particle). Heat may not be very effective and the likelihood that you eliminate all the prions to the point that they'd have no effect is lower.

ben_w 6y ago
Also not a chemist, but you’ve made me notice my confusion: Aren’t proteins generally easy to denature? Isn’t that what most cooking does? And what alcohol does?
- davesque 6y ago
  No idea, honestly. As I mentioned, I'm not an expert.
- subungual 6y ago
  So denaturing a protein generally involves interfering with the noncovalent interactions (e.g. hydrogen bonds, attractions between internal charges) that allow it to fold into the right functional shape. Often times, these proteins folded under conditions that carefully facilitated their coming out the right way, so simply removing the denaturing stimulus (e.g. allowing them to cool) won't result in a reversion to their former configuration. This is what you see, for example, in cooking, where there's a discrete change that doesn't revert. Prions are generally much more stable and can revert back to dangerous form once denaturing conditions change back. It takes a lot more to denature them irreversibly than it does most proteins. This stability is part of what makes them so dangerous and difficult to remove.
  - dwohnitmok 6y ago
    > Prions are generally much more stable and can revert back to dangerous form once denaturing conditions change back. Indeed I'd imagine that almost definitionally prions must be difficult to denature. Since they are non-living and therefore have no way of "seeking out food," durability is the only way they can compete for reproduction. That is they can only become infectious if their resistance to denaturing was sufficiently high to resist environmental damage until their next target comes around.
    - ben_w 6y ago
      It’s unusual to discuss a non-living chemical in terms of reproductive fitness, but I guess the word fits…
      - monoideism 6y ago
        There is currently no consensus on what constitutes a living thing. Some include viruses, some not. Most do not include prions, but prions do feature many of living things (eg, they evolve, adapt to their environment, replicate, etc).
    - subungual 6y ago
      Yeah, your logic is pretty good here. Prions are a super interesting emergent phenomenon of a complex system. In a weird way, like cancer or viruses, they're just an inevitability of having enough of certain materials interacting for long enough time. Proteins misfold in just such a way that allows them to induce the same type of misfolding in other proteins, leading to propagation. It's less a definitional thing, and more a matter of the fact that something more stable will persist longer, encounter more opportunities to propagate and preserve its form. That said, surviving harsh environments isn't an entirely necessary condition, as not all prion generation requires transmission. Unfortunately, if you have the wrong gene(s) broken, you're at risk of just generating them yourself. That said, transmission is significant, and since it involves needing to be able to survive a harsh outside environment with no propagation between hosts, extreme durability is a definite boon, as you suggest.
- JauntTrooper 6y ago
  Here's an article on it: https://www.scientificamerican.com/article/surgical-exposure-to-cjd-prion/ https://www.scientificamerican.com/article/surgical-exposure...
- theideaofcoffee 6y ago
  Another commenter pointed out that the general idea of denaturing a protein is interfering with noncovalent interactions, generally by interrupting the structure that the complete sequence takes after the folding process. These structures give rise to the classic shapes that proteins take, the loops and sheets and clumps of atoms you see in renderings. The other commenter mentioned cooking, and this process is the same that happens when you cook an egg, the proteins in the egg white are denatured and turn into amorphous strands of protein. However there is a difference between a denaturing process and a lysing (breaking) process, meaning that the actual covalent, chemical bonds between the component amino acids that make up a protein are broken. This bond is called the peptide bond, and they are extremely stable, and to break them without enzymes requires some crazy conditions like strong acids or bases and high heat and long periods of time. There is a class of enzymes called proteases that catalyze and speed up this breaking-down process, which is what cells use to digest and break down proteins.
- dnautics 6y ago
  OK, so I worked seven years in this field. Prions (and amyloid diseases in general, like alzheimer's, diabetes, and a ton of diseases you probably haven't heard of [0]) happen when a "normally folded protein" denatures into a flat ribbon [1]. These ribbons become a sheet when you get many of them side-by-side, and this it turns out is an extremely stable configuration. Also, it's autocatalytic (exponential growth), because these sheets will fragment and recruit well-folded proteins (that are of the same molecule) to become ribbons at their ends, extending and growing the sheet. So, yes, it is protein denaturation. But it's a very specific denaturation endpoint that not all proteins are capable of, and it's such a favored endpoint that even heating won't quantitatively destroy it (and heating could make it worse by fragmenting it into a bunch of smaller sheets). [0] Incidentally, this denaturation is probably also used by cells in a productive fashion, it's pretty likely IMO that your melanin cells use these sheets to template melanin formation and sequester away the melanin molecule (the melanin precursor is highly toxic). I would link to the paper, but I think all of the data have been essentially cherry picked from shittily-done experiments, even though I think their conclusion is correct -- I have personally repeated the experiments "correctly" and reached the same endpoints in one shot without cherry picking (unpublished for my experiment, also n == 1) -- so I don't want to draw more unhealthy attention to the paper until someone else does the experiment "correctly". [1] how does this happen? It can happen either due to a mutation that destabilizes the parent, well-folded protein, or, just by bad luck / time. Mutation examples: Fatal Familial Insomnia, non-variant CJD. Bad luck/Time example, insulin in a bottle in a fridge will turn into white flecks (these are sheets). The time at which this happens is highly variable (luck). You can accelerate this by agitating the bottle, and creating an air-water surface that catalyzes the denaturation of insulin. Also note, that insulin is not the protein in sheets in diabetes :biology trollface: (the insulin situation is strictly in vitro, and pH-dependent, as far as we can tell)
  - greenwich26 6y ago
    Probably a very ignorant question, but don't protease enzymes break proteins down to the amino acids? Suppose my lab bench is infected with prions or flat protein sheets or something. If I spray it over with a bunch of protease, would I be able to "disinfect" it?
deleted 6y ago
[deleted]

ben_w 6y ago

Also not a chemist, but you’ve made me notice my confusion: Aren’t proteins generally easy to denature? Isn’t that what most cooking does? And what alcohol does?

davesque 6y ago
No idea, honestly. As I mentioned, I'm not an expert.
subungual 6y ago
So denaturing a protein generally involves interfering with the noncovalent interactions (e.g. hydrogen bonds, attractions between internal charges) that allow it to fold into the right functional shape. Often times, these proteins folded under conditions that carefully facilitated their coming out the right way, so simply removing the denaturing stimulus (e.g. allowing them to cool) won't result in a reversion to their former configuration. This is what you see, for example, in cooking, where there's a discrete change that doesn't revert. Prions are generally much more stable and can revert back to dangerous form once denaturing conditions change back. It takes a lot more to denature them irreversibly than it does most proteins. This stability is part of what makes them so dangerous and difficult to remove.
- dwohnitmok 6y ago
  > Prions are generally much more stable and can revert back to dangerous form once denaturing conditions change back. Indeed I'd imagine that almost definitionally prions must be difficult to denature. Since they are non-living and therefore have no way of "seeking out food," durability is the only way they can compete for reproduction. That is they can only become infectious if their resistance to denaturing was sufficiently high to resist environmental damage until their next target comes around.
  - ben_w 6y ago
    It’s unusual to discuss a non-living chemical in terms of reproductive fitness, but I guess the word fits…
    - monoideism 6y ago
      There is currently no consensus on what constitutes a living thing. Some include viruses, some not. Most do not include prions, but prions do feature many of living things (eg, they evolve, adapt to their environment, replicate, etc).
  - subungual 6y ago
    Yeah, your logic is pretty good here. Prions are a super interesting emergent phenomenon of a complex system. In a weird way, like cancer or viruses, they're just an inevitability of having enough of certain materials interacting for long enough time. Proteins misfold in just such a way that allows them to induce the same type of misfolding in other proteins, leading to propagation. It's less a definitional thing, and more a matter of the fact that something more stable will persist longer, encounter more opportunities to propagate and preserve its form. That said, surviving harsh environments isn't an entirely necessary condition, as not all prion generation requires transmission. Unfortunately, if you have the wrong gene(s) broken, you're at risk of just generating them yourself. That said, transmission is significant, and since it involves needing to be able to survive a harsh outside environment with no propagation between hosts, extreme durability is a definite boon, as you suggest.
JauntTrooper 6y ago
Here's an article on it: https://www.scientificamerican.com/article/surgical-exposure-to-cjd-prion/ https://www.scientificamerican.com/article/surgical-exposure...
theideaofcoffee 6y ago
Another commenter pointed out that the general idea of denaturing a protein is interfering with noncovalent interactions, generally by interrupting the structure that the complete sequence takes after the folding process. These structures give rise to the classic shapes that proteins take, the loops and sheets and clumps of atoms you see in renderings. The other commenter mentioned cooking, and this process is the same that happens when you cook an egg, the proteins in the egg white are denatured and turn into amorphous strands of protein. However there is a difference between a denaturing process and a lysing (breaking) process, meaning that the actual covalent, chemical bonds between the component amino acids that make up a protein are broken. This bond is called the peptide bond, and they are extremely stable, and to break them without enzymes requires some crazy conditions like strong acids or bases and high heat and long periods of time. There is a class of enzymes called proteases that catalyze and speed up this breaking-down process, which is what cells use to digest and break down proteins.
dnautics 6y ago
OK, so I worked seven years in this field. Prions (and amyloid diseases in general, like alzheimer's, diabetes, and a ton of diseases you probably haven't heard of [0]) happen when a "normally folded protein" denatures into a flat ribbon [1]. These ribbons become a sheet when you get many of them side-by-side, and this it turns out is an extremely stable configuration. Also, it's autocatalytic (exponential growth), because these sheets will fragment and recruit well-folded proteins (that are of the same molecule) to become ribbons at their ends, extending and growing the sheet. So, yes, it is protein denaturation. But it's a very specific denaturation endpoint that not all proteins are capable of, and it's such a favored endpoint that even heating won't quantitatively destroy it (and heating could make it worse by fragmenting it into a bunch of smaller sheets). [0] Incidentally, this denaturation is probably also used by cells in a productive fashion, it's pretty likely IMO that your melanin cells use these sheets to template melanin formation and sequester away the melanin molecule (the melanin precursor is highly toxic). I would link to the paper, but I think all of the data have been essentially cherry picked from shittily-done experiments, even though I think their conclusion is correct -- I have personally repeated the experiments "correctly" and reached the same endpoints in one shot without cherry picking (unpublished for my experiment, also n == 1) -- so I don't want to draw more unhealthy attention to the paper until someone else does the experiment "correctly". [1] how does this happen? It can happen either due to a mutation that destabilizes the parent, well-folded protein, or, just by bad luck / time. Mutation examples: Fatal Familial Insomnia, non-variant CJD. Bad luck/Time example, insulin in a bottle in a fridge will turn into white flecks (these are sheets). The time at which this happens is highly variable (luck). You can accelerate this by agitating the bottle, and creating an air-water surface that catalyzes the denaturation of insulin. Also note, that insulin is not the protein in sheets in diabetes :biology trollface: (the insulin situation is strictly in vitro, and pH-dependent, as far as we can tell)
- greenwich26 6y ago
  Probably a very ignorant question, but don't protease enzymes break proteins down to the amino acids? Suppose my lab bench is infected with prions or flat protein sheets or something. If I spray it over with a bunch of protease, would I be able to "disinfect" it?

deleted 6y ago

[deleted]