Loops to tie a knot in proteins?
Most proteins fold onto themselves without forming knots. A minority form a ’topologically entangled conformation’, a knot.
Proteins are strings of amino acids, chained together one after the other.
The properties of proteins depends on their specific three-dimensional fold, how the chain of amino acids are arranged in space.
When proteins are first made by reading the RNA copy of a gene, the order of the adjacent triplets of RNA bases (letters of the RNA code) specify a specific order of amino acids, one amino for each particular triplet of bases.
This initial chain of amino acids is just that, a linear chain.
Proteins fold through the physical properties of the particular sequence of amino acids making up the protein inducing a particular collapsing of the protein on itself in water.
For the vast majority of proteins this collapsing on itself does not involves a portion of the chain threading itself through another portion of the chain to form a knot.
Intuitively this makes sense; self-knotting of a protein chain would be more finicky that simply placing portions of chain adjacent to other portions of the chain.
A few proteins, however, manage to pull off this self-knotting feat.
Being able to accurately predict the folding of a protein from it’s amino acid sequence, to solve the ’protein folding problem’ would open door to designer enzymes and vastly increase our understanding of life through having available the detailed chemical arrangement of proteins in 3-D.
Examining knotted proteins, with their potentially more finicky folding requirements, might be another way to explore the detailed basis protein folding.
What features might guide self-knotting in proteins and can they teach us something about how proteins fold?
European computational biologists compared proteins that form knots and those that do not, looking for features that might be associated with knot formation.
For the most part the amino acid sequence of the proteins did not distinguish knotted proteins from those without knots.
Comparing the 3-D structures of proteins, in particular those with similar overall folds but with one case being knotted and the other not, their work suggested particular loops on the surface of some the proteins examined are a feature common to knotted proteins not found in unknotted proteins.
These might be, in their words, ’knot-promoting’ loops, in some way these loops may be aiding the chain in threading through itself.
I’ve no doubt that researchers will now look very closely at these particular protein loops and see if they do in fact promote the formation of a protein knot.
Potestio, R., Micheletti, C., & Orland, H. (2010). Knotted vs. Unknotted Proteins: Evidence of Knot-Promoting Loops PLoS Computational Biology, 6 (7) DOI: 10.1371/journal.pcbi.1000864
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0 Responses to “Loops to tie a knot in proteins?”
I love this area of biology. I got quite addicted to this “video game” a couple of years back: –
http://fold.it/
As a teacher, I’ve tried to get a couple of students into it as well. Playing games and helping science at the same time!
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Thanks for sharing this Paul. I saw this when it was first announced, but haven’t looked at it again since. Great to hear that you’re encouraging your students to play with it.
You might like to know the fold-it team have a Nature paper on the way out: http://fold.it/portal/node/987897
Apparently it has 75,000 authors…
I think we can safely say that Nature is not going to list all the authors!
I’ll probably have something to say about it when it’s available.
I was going to write my own take on the Nature FoldIt paper, but there is such a slew of articles about it on the ‘web I’m not sure another one would really be of use to anyone. Do say so, though, if there is some aspect of it you’d like me to cover.
I have to admit when I saw the advance notice in my previous comment, I though this would be one where having access to the embargo would help! (As some science writers who also blog do; I don’t. Yet!)
Anyway, here’s one take on it at ArsTechnica:
http://arstechnica.com/science/news/2010/08/gamers-beat-algorithms-for-finding-protein-structures.ars
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