I am new to the field of biochemistry (I am a chemist, actually).

I have long known the process of folding as the process that leads to the minimum energy conformation of a protein.

Now, I am introduced to the chaperones, that I didn't know before.

What I am wondering is: my previous view of folding, as a proces of "self-assembly" (the protein folds without external assistance as it is assembled by the ribosome) is real, or any folding process is assisted by chaperones?

If both processes exist, how frequent is the "assisted" folding, compared to the spontaneous process?

  • $\begingroup$ I've edited your title to remove the word "frequent" as what you are asking is not a temporal question (how many proteins per minute are folded with chaperones) but one of proportion or description (do all proteins are just some fold in this way). Do revert or modify if you don't like my change. $\endgroup$ – David Jul 22 '18 at 14:55

I'm reminded of a lovely review in Trends in Biochemical Sciences that discusses chaperone independent, partially dependent, and fully dependent proteins in prokaryotes. The conclusion was that smaller polypeptides are less likely to require chaperone assistance. This is their figure:

enter image description here

That principle still holds to a certain extent (in prokaryotes), but folding assistance is now more broadly understood to include much more than just specific proteins identified as molecular chaperones. The Anfinsen postulate (that the final tertiary structure of a protein depends only on its primary structure) may still hold for small globular proteins, but folding in vivo is almost certainly always assisted. Since you're coming from the perspective of a chemist, don't think of it as a reaction between two molecules in solution. It's a reaction in a gel packed with complex sugars, lipids, proteins, and nucleic acids.

If you're skeptical of the perspective of a crowded cytoplasm, read the review I linked. It's an important but often under-appreciated aspect of in vivo biochemistry. There is much more to read about it. You might try looking up Allen Minton (AP Minton) and macromolecular crowding in your favorite database.

  • $\begingroup$ I would upvote your answer, but for the last two sentences. If the cytoplasm is "a gel completely packed with things" how do tRNAs, protein synthesis factors etc. diffuse to the ribosomes, and the released proteins distribute themselves in the cytoplasm. And what precisely has this to do with the protein folding? This is a serious, not a rhetorical, question. $\endgroup$ – David Jul 21 '18 at 22:05
  • $\begingroup$ @David did you read the serious, not rhetorical paper I referenced? $\endgroup$ – De Novo Jul 21 '18 at 22:22
  • $\begingroup$ @David on re-reading, i may have phrased it a little stronger than I should have in order to emphasize the difference between dilute in-vitro biochemistry and the gel-like phase where protein biochemistry (including folding) occurs in-vivo. I removed the word completely, and added a comment about it. $\endgroup$ – De Novo Jul 21 '18 at 23:41
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    $\begingroup$ — I'll check your reference out. I'm traveling in a foreign country where I'm being charged a £7 per Mb for data, so I'm dependent on rather flaky wifi reception. $\endgroup$ – David Jul 22 '18 at 1:32
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    $\begingroup$ Ok, I've looked at both the TIBS review and the 2012 Int J Mol Sci review. I see that the latter makes the point that the results in vitro are not always borne out by those in vitro (e.g. with mutants in the chaperones) and the authors suggest that (non-specific?) interactions with other molecules may be important. That's all I see that relates to your "gel" remark, which I now see you've clarified in your answer. The general impression I get is that it's difficult to answer the question posted with any precision, although assisted folding cetainly exists. $\endgroup$ – David Jul 22 '18 at 14:51

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