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If molecular chaperone proteins assist in the folding process of other proteins and misfolded proteins, can chaperone themselves misfold since they are also proteins? What would happen if chaperones misfolded? Can they misfold at all? Why or why not?

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    $\begingroup$ Someone proposed this interesting hypothesis that misfolded chaperones can misfold other proteins and/or create more misfolded chaperones. Thus prions may be some kind of misfolded chaperones. $\endgroup$ – WYSIWYG Feb 21 at 10:20
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Chaperone proteins are still proteins and they can certainly misfold just like any other. If that happens, it will either be assisted by another chaperone and given time to fold successfully or it will be destroyed. If this is happening too often and the amount of chaperones drops too low or the number of unfolded or incorrectly folded proteins becomes excessive*, the unfolded protein response may be triggered and, if it does not resolve the issue and the cell remains stressed, the cell will undergo apoptosis and die.

Some chaperones, especially heat-shock proteins, may be more resistant to misfolding. This is true because they need to be able to withstand noxious conditions that denature other proteins. Not all chaperones are resistant to heat though and many are no more intrinsically resistant to denaturing.

* It's not uncommon for a "bad" batch of proteins to be created. This can happen with a transcription error during mRNA synthesis since each mRNA molecule is read by many ribosomes. This can naturally happen with chaperones as well.

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  • $\begingroup$ Good answer but it would be great if you can add some references for chaperones rescuing other misfolded chaperones. If you cannot find references (which, for this topic, I can understand) then you can indicate that this is your speculation. $\endgroup$ – WYSIWYG Feb 21 at 9:47
  • $\begingroup$ @WYSIWYG Many chaperones are non-specific in their interactions. For some reason I'm unable to access NIH right now (my IP is blocked), but a search shows examples of non-specific chaperone-mediated folding. $\endgroup$ – forest Feb 21 at 10:40
  • $\begingroup$ researchgate.net/post/… $\endgroup$ – forest Feb 21 at 10:46
  • $\begingroup$ I did a search on this topic myself but could not find any resourceful articles (researchgate is as good as stackexchange and even it doesn't have conclusive answers on this topic). So, I won't blame you. $\endgroup$ – WYSIWYG Feb 21 at 11:05

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