"In proteins, the three-dimensional structure is very important to the function, and this is just one example," said Peter Virnau, a postdoctoral fellow in physics and an author of a paper on the work that appears in the Sept. 15 issue of the Public Library of Science, Computational Biology.
Knots are rare in proteins - less than 1 percent of all proteins have any knots, and most are fairly simple. The researchers analyzed 32,853 proteins, using a computational technique never before applied to proteins at this scale.
Of those that had knots, all were enzymes. Most had a simple three-crossing, or trefoil knot, a few had four crossings, and the most complicated, a five-crossing knot, was initially found in only one protein - ubiquitin hydrolase.
That complex knot may hold some protective value for ubiquitin hydrolase, whose function is to rescue other proteins from being destroyed - a dangerous job.
When a protein in a cell needs to be destroyed, it gets labeled with another protein called ubiquitin. "It's a death mark for the protein," said Leonid Mirny, an author of the paper and an associate professor in the MIT-Harvard Division of Health Sciences and Technology.
Once the "death mark" is applied, proteins are shuttled to a cell structure called a proteasome, which pulls the protein in and chops it into pieces. However, if ubiquitin hydrolase intervenes and removes the ubiquitin, the protein is saved.
The complicated knot found in ubiquitin hydrolase may prevent it from getting sucked into the proteasome as it works, Mirny said. The researchers hypothesize that proteins with complex knots can't be pulled into the proteasome as easily, and the knots may make it harder for the protein to unfold, which is necessary fo
Source:Massachusetts Institute of Technology