mRNA / tRNA / rRNA and folding

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mRNA / tRNA / rRNA and folding

Postby stevedking » Sun Dec 30, 2012 8:10 am

Does the rRNA link the amino acids together in linear sequential order from 1st amino acid to nth amino acid, or... does the rRNA create segments of the protein in random order (directed by mRNA) --- then assemble the final protein by linking all segments together --- similar to the way packets are assembled in an email message?
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Re: mRNA / tRNA / rRNA and folding

Postby stevedking » Sun Dec 30, 2012 8:25 pm

stevedking wrote:Does the rRNA link the amino acids together in linear sequential order from 1st amino acid to nth amino acid, or... does the rRNA create segments of the protein in random order (directed by mRNA) --- then assemble the final protein by linking all segments together --- similar to the way packets are assembled in an email message?



What I'm implying is the following:
1. Let's take a dummy protein with the following amino acid sequence [ABCDEF] for demo purpose.

CASE (A). [AB] is constructed first, then [CDEF], then finally both segments are joined [ABCDEF] and the protein folds correctly.

CASE (B). [ABCD] is constructed first, then [EF], then finally both segments are joined [ABCDEF] and the protein folds incorrectly.

I am starting to believe that the order in which strand segments of the protein are made, then joined, is the root cause of improper protein folding. The order in which segments are made, and the segments themselves (see Case (A) and Case (B)), may make the overall protein more affected by environmental factors such as temperature --- or the protein itself may have weaker forces.


Just a thought.
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Re: mRNA / tRNA / rRNA and folding

Postby Jesse_V » Sun Dec 30, 2012 8:41 pm

mRNA comprises a series of codons that dictate to the ribosome the sequence of the amino acids needed to make the protein. The ribosome assembles the protein one amino acid at a time, and the protein folds as the ribosome assembles it. The ribosome is a really big assemblage of proteins and other molecules, and one of its components is the exit tunnel, through which the protein emerges as it is being created. This implies that the protein is at least partially inside the tunnel as it folds, which raises the question: does the tunnel influence the folding process? If you search the papers page (http://folding.stanford.edu/English/Papers) you'll see studies into the role of confinement and its effects into protein folding.
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Re: mRNA / tRNA / rRNA and folding

Postby bruce » Sun Dec 30, 2012 11:16 pm

stevedking wrote:CASE (A). [AB] is constructed first, then [CDEF], then finally both segments are joined [ABCDEF] and the protein folds correctly.

CASE (B). [ABCD] is constructed first, then [EF], then finally both segments are joined [ABCDEF] and the protein folds incorrectly.

I am starting to believe that the order in which strand segments of the protein are made, then joined, is the root cause of improper protein folding.


Suppose we wait until ABCDEF has been constructed (using either method) and we note the position of every atom. Give that data to a scientist and ask him to figure out whether it was constructed as ABCD+EF or as AB+CDEF. How will he be able to tell the difference?

At time=0, FAH is going to assume some unfolded shape for ABCDEF and study it's progress toward a folded state. It won't know or care what happened for time < 0. The same is true for much of the work done by MSM models. The protein folding process may start at some common intermediate shape and progress toward a folded state by several possible pathways, but how it got to that particular starting shape won't necessarily be part of that same study.
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Re: mRNA / tRNA / rRNA and folding

Postby Jesse_V » Mon Dec 31, 2012 2:12 am

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Re: mRNA / tRNA / rRNA and folding

Postby stevedking » Mon Dec 31, 2012 4:42 am

Jesse_V and Bruce,

Thanks very much --- this is clearer to me now. I'll just let my machine fold ... and if I come up with anymore questions, I'll just ask or do a bit more reading in the FAQ or Papers. Protein folding is very interesting.
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