MIT scientists have identified a protein that contains five knots, which is an extremely rare occurrence, and now they believe they know the reason behind this complicated structure. The research was published in PLoS Computational Biology.
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 for degradation.
The same knot is found in ubiquitin hydrolase in humans and in yeast, supporting the theory that there is a connection between the knot and the protein’s function. This also seems to suggest that the knot has been “highly preserved throughout evolution,” Virnau said.
Until now, scientists have not paid much attention to knots in proteins, but the MIT researchers hope their work will ignite further interest in the subject…
Since their initial screening, the researchers have discovered five-crossing knots in two other proteins–a brain protein, whose overexpression and mutations are linked with cancer and Parkinson’s disease, and a protein involved in the HIV replication cycle.