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What makes sure chaperonins fold correctly?

  1. Oct 11, 2011 #1
    Disease states such as AZ and Huntington's are thought to be related to amyloid plaques resulting from proteins that are misfolded. Chaperonins assist to make sure proteins fold correctly as well as unzip misfolded proteins to give them a second chance at folding properly. So my question is this, what makes sure that the chaperonins themselves fold correctly? Are there chaperonins of chaperonins? If so, what would make sure chaperonins of chaperonins fold correctly (of course you could keep continuing this logic)? Rather than studying the misfolding and polymerization of misfolded proteins that lead to amyloids, has anyone done research on whether or not the chaperonins that are supposed to be regulating the misguided protein folding are themselves misfolded?
     
  2. jcsd
  3. Oct 11, 2011 #2

    bobze

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    Amyloids that result in amyloidosis are often the result of mutated proteins, which changes their primary structure and thus subsequent structures.

    Many chaperones aren't actually "refolding" proteins, rather hydrolyzing bonds and allowing them a chance "refold" on their own--Such as protein disulfide isomerases.

    Lots of large cytoplasmic chaperones are multimeric in constitution and it seems plausible to me that individual subunits would require (sometimes at least) the aid of already folded chaperones. However, I think that is a simple way of looking at it, not all proteins require chaperones to fold and even ones that do don't always need a chaperone all the time.

    Both diseases you list are complex diseases that have a host of other affecting factors that can cause protein precipitation. Huntington's, while were not sure what exactly the protein does (at least, I believe it still hasn't been discovered yet), we do know the genetics that effect the protein--It is from CAG repeats expressed in the gene. Like other expanded triplet nucleotide disease it shows genetic anticipation--Becoming worse in subsequent generations in both age of onset and disease severity (well with Huntington's its always severe as death is the result, I guess dying younger would be "more severe"). Anyway, the point here is like other TNR diseases the introduction of more repeats is what causes the dysfunctional proteins, something a chaperon wouldn't be able to correct.
     
  4. Oct 12, 2011 #3
    Like Bobze said, many proteins do not need chaperones at all in order to correctly fold into their shape. And some chaperones are involved in their own assembly.
     
  5. Oct 12, 2011 #4
    So there are no examples of misfolded chaperonins that cause the proteins that they chaperon to misfold? (sort of like a chicken or egg game I'm playing with myself I suppose)

    Thanks for the replies.
     
  6. Oct 13, 2011 #5
    A google search showed an interesting result.

    http://www.ncbi.nlm.nih.gov/pubmed/1756852
     
  7. Oct 17, 2011 #6
    I read a few papers and there are actually many types of chaperonins. Some chaperonins likely help fold other chaperonins. Proteins do not always misfold, so there is a good chance that a chaperonin class could aid in its own folding.

    Its a good question - what can happen if chaperonins pick up some kind of mutation which makes them overactive. Chaperonins are important in maintaining highly mutated proteins, and there are studies which show that cancer lines tend to pick up chaperonin overexpression in order to compensate for their higher mutation levels.
     
  8. Oct 19, 2011 #7
    Right. Chaperones are therefore also said to have a buffering mechanism that dampens the effect of rapid genetic variation due to mutation, although it may not always be due to the stabilization of the protein in question.


    www.ncbi.nlm.nih.gov/pubmed/15077153
     
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