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I'm curious, if it's a "misfolding protein" (my knowledge of biology is not sufficient to know what "misfolding" means here, I understand that proteins fold, bu

I'm curious, if it's a "misfolding protein" (my knowledge of biology is not sufficient to know what "misfolding" means here, I understand that proteins fold, but "misfolding" is a mystery to me), then what is the reproducing mechanism? My understanding is that viruses reproduce themselves by hijacking the DNA (or RNA?) in cells. DNA being a cell reproduction mechanism that copies protein structures. But what is it about a particular protein that can make itself reproduce and infect the body?

genocidicbunny 5y ago
My (admittedly, very layman) understanding is that prions are proteins that are misfolded in such a way that when in proximity or contact with their 'correctly folded' version can induce them to change shape to the misfolded version. Prions are below the level of things like viruses or bacteria -- they are a result of the underlying chemistry of making proteins. Proteins and their folding is arranging atoms into energetically favorable states. A prion is then a different arrangement of the atoms that is somewhat more energetically favorable, one that can induce other proteins to transition to this different state. It is this last property that makes them infectious.
adammunich 5y ago
It catalyzes others like ice-9
teachingassist 5y ago
Proteins are produced as a string (either literally as a chain molecule, or in the computer science sense of a string of characters/amino acids). Once a protein is formed in the body, it naturally folds into its useful, functional shape with the purpose it was designed for. A 'misfolding protein' is then a folding into a stable shape which is not desired. A 'prion' is a misfolding protein that encourages other proteins of the same type to misfold in the same way - maybe by acting as an incorrect template for folding. When this is folded in a way that is difficult for the body to break down, and somehow enabling its sibling proteins to do the same, you start to have problems. So, a prion is a protein structure able to reproduce itself, in some way. Prions are not 'viruses', where viruses have their own DNA (or RNA) for making their own proteins. There's an argument about whether viruses are 'alive', since they depend on others' cells to make their proteins. Prions are even less considered 'alive' - they are just inert single protein molecules folded in a particular way. But, they have the ability to reproduce, in some sense.
- string 5y ago
  I've tried to read about prions a few times and never really grasped the mechanism, so this was a really informative explanation, thank you.
  - TeMPOraL 5y ago
    In terms of folding, you can imagine a protein as balls on a string, where each ball has some extra stuff on its surface. One may have a bit of velcro hooks here and a small magnet there (N outwards). Another one may have some surface adhesive and a S-outwards magnet. Another one, velcro loops and a blob of adhesive. Etc. You put such a string of balls in a box and shake it for a while. After you're done, you'll have a somewhat stable structure made of various balls connected by their relevant attachment mechanisms. If you were clever at designing the original string of balls, you could make it highly probable that any such string would reach the same connected structure after being tumbled a bit. Proteins are like that. The connections are chemical bonds; velcro, magnets and glue represent different structures on protein pieces that allow some kids of bonds to form with given strengths, and disallow others. The tumbling/shaking part is matter and temperature - in a living organism, everything mostly keeps bumping into everything else at random, and in particular, there's plenty of water molecules to push things around randomly. Pieces of protein thus keep connecting and disconnecting with other pieces, until the whole molecule reaches a stable state where the constant bumping isn't enough to break any of the bonds. That's how proteins fold. Somehow, it turns out that any given protein tends to almost always fold into a very specific shape (which is currently impossible for us to compute a-priori, given just an ordered list of amino acid residues). But there are other possible shapes that a protein can sometimes reach, which are also stable but do not let it perform the functions the body needs it to. That's bad - such a protein is at best useless, at worst disruptive, and stability makes it hard for the body to get rid of it. Then there sometimes are stable shapes whose presence cause other similar proteins to fold to that same shape, instead of the one they'd ordinarily do - that's prions. That's very bad news. They reproduce through catalyzing creation of more of them, and their stability means they can just linger around after the host organism has died, and it's not easy to destroy them through boiling or denaturing agents.
indiv0 5y ago
It’s not just a misfolded protein, it’s a misfolded protein that catalyzes other proteins (with the same chemical structure) to misfold. So proximity of a “good” protein to a “bad” protein is sufficient to turn the “good” protein “bad”. It’s an interesting hypothesis to consider that there could be other prion variations out there that misfold other types of proteins, but they don’t misfold the “good” versions of themselves, so they don’t self-replicate and instead just create one-off instances of a broken protein.
- radarsat1 5y ago
  Huh, that's very interesting. I certainly didn't know that protein folding could be influenced by other proteins around them; I guess I sort of thought that proteins and their structure were fully defined by DNA. But it makes sense.. if a particular folding has an unstable point (ie., could go one way or another), it would naturally be influenced by the forces around it in addition to its "code". Thanks for the insight!
  - Doxin 5y ago
    There's even specific "chaperone" proteins that help more complex proteins fold correctly. Biology is pretty wild like that :P

genocidicbunny 5y ago

My (admittedly, very layman) understanding is that prions are proteins that are misfolded in such a way that when in proximity or contact with their 'correctly folded' version can induce them to change shape to the misfolded version. Prions are below the level of things like viruses or bacteria -- they are a result of the underlying chemistry of making proteins. Proteins and their folding is arranging atoms into energetically favorable states. A prion is then a different arrangement of the atoms that is somewhat more energetically favorable, one that can induce other proteins to transition to this different state. It is this last property that makes them infectious.

adammunich 5y ago

It catalyzes others like ice-9

teachingassist 5y ago

Proteins are produced as a string (either literally as a chain molecule, or in the computer science sense of a string of characters/amino acids). Once a protein is formed in the body, it naturally folds into its useful, functional shape with the purpose it was designed for. A 'misfolding protein' is then a folding into a stable shape which is not desired. A 'prion' is a misfolding protein that encourages other proteins of the same type to misfold in the same way - maybe by acting as an incorrect template for folding. When this is folded in a way that is difficult for the body to break down, and somehow enabling its sibling proteins to do the same, you start to have problems. So, a prion is a protein structure able to reproduce itself, in some way. Prions are not 'viruses', where viruses have their own DNA (or RNA) for making their own proteins. There's an argument about whether viruses are 'alive', since they depend on others' cells to make their proteins. Prions are even less considered 'alive' - they are just inert single protein molecules folded in a particular way. But, they have the ability to reproduce, in some sense.

string 5y ago
I've tried to read about prions a few times and never really grasped the mechanism, so this was a really informative explanation, thank you.
- TeMPOraL 5y ago
  In terms of folding, you can imagine a protein as balls on a string, where each ball has some extra stuff on its surface. One may have a bit of velcro hooks here and a small magnet there (N outwards). Another one may have some surface adhesive and a S-outwards magnet. Another one, velcro loops and a blob of adhesive. Etc. You put such a string of balls in a box and shake it for a while. After you're done, you'll have a somewhat stable structure made of various balls connected by their relevant attachment mechanisms. If you were clever at designing the original string of balls, you could make it highly probable that any such string would reach the same connected structure after being tumbled a bit. Proteins are like that. The connections are chemical bonds; velcro, magnets and glue represent different structures on protein pieces that allow some kids of bonds to form with given strengths, and disallow others. The tumbling/shaking part is matter and temperature - in a living organism, everything mostly keeps bumping into everything else at random, and in particular, there's plenty of water molecules to push things around randomly. Pieces of protein thus keep connecting and disconnecting with other pieces, until the whole molecule reaches a stable state where the constant bumping isn't enough to break any of the bonds. That's how proteins fold. Somehow, it turns out that any given protein tends to almost always fold into a very specific shape (which is currently impossible for us to compute a-priori, given just an ordered list of amino acid residues). But there are other possible shapes that a protein can sometimes reach, which are also stable but do not let it perform the functions the body needs it to. That's bad - such a protein is at best useless, at worst disruptive, and stability makes it hard for the body to get rid of it. Then there sometimes are stable shapes whose presence cause other similar proteins to fold to that same shape, instead of the one they'd ordinarily do - that's prions. That's very bad news. They reproduce through catalyzing creation of more of them, and their stability means they can just linger around after the host organism has died, and it's not easy to destroy them through boiling or denaturing agents.

indiv0 5y ago

It’s not just a misfolded protein, it’s a misfolded protein that catalyzes other proteins (with the same chemical structure) to misfold. So proximity of a “good” protein to a “bad” protein is sufficient to turn the “good” protein “bad”. It’s an interesting hypothesis to consider that there could be other prion variations out there that misfold other types of proteins, but they don’t misfold the “good” versions of themselves, so they don’t self-replicate and instead just create one-off instances of a broken protein.

radarsat1 5y ago
Huh, that's very interesting. I certainly didn't know that protein folding could be influenced by other proteins around them; I guess I sort of thought that proteins and their structure were fully defined by DNA. But it makes sense.. if a particular folding has an unstable point (ie., could go one way or another), it would naturally be influenced by the forces around it in addition to its "code". Thanks for the insight!
- Doxin 5y ago
  There's even specific "chaperone" proteins that help more complex proteins fold correctly. Biology is pretty wild like that :P