November 18, 2008 | David F. Coppedge

Proteins Can Tie Knots

Your job today is to invent a chain that can tie itself in a knot.  The chain can contain little magnets and electrical parts, but when you let go of the ends, a knot will spontaneously form.  This means that one end must form a loop and the other end must thread the loop.  Give up?  Maybe you should learn how cells do it.
    There are certain chains of amino acids coming out of the ribosome translation machine that will tie a perfect trefoil knot (picture) every time.  This knot becomes embedded deep within the overall structure of the protein.  A trio of women scientists at the University of Pennsylvania School of Medicine tried to figure this out.  Writing in PNAS,1 they only made small progress.  All they could say was that the knot tying seems to occur early on, when the chain is loose.  The tightening of the knot and the rest of the folding occurs slowly thereafter.  They mutated certain amino acids to watch what happened but that’s about all they could figure out at this point.
    The protein they studied, YibK, is one of the simplest knot-tying proteins.  They mentioned others with even bigger tricks:

The alpha/beta-knot methyltransferases (MTases) are a family of homodimeric proteins that exhibit an unusual trefoil knot deep within in their native structure.  Such knots are particularly impressive because they are defined by the path of the polypeptide backbone alone and therefore require that a considerable segment of protein chain (at least 40 residues) has threaded through a loop.  The question of how such complex topologies arise during protein folding is an intriguing one, and is of growing importance with the increasing number and complexity of knotted structures observed.  In addition to trefoil knots, a highly intricate figure-of-eight knot and a knotted structure with 5 projected crossings have been observed.  Consequently, when contemplating how a given polypeptide chain might fold, the possibility that it might knot must also be considered; if a global solution to the protein-folding problem is to be found, the puzzle of how such knotted structures form must be solved.

Evolutionary theory played no role in their investigation.


1.  Anna L. Mallam, Elizabeth R. Morris, and Sophie E. Jackson, “Exploring knotting mechanisms in protein folding,” Proceedings of the National Academy of Sciences, USA, published online before print November 17, 2008, doi: 10.1073/pnas.0806697105.

A protein that can tie a figure-of-eight knot (picture) blindfolded with no hands: amazing.  The Darwinians can’t even do that eyes-open with their baloney.

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