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. "We just hope this will become a part of the routine crystallographers and NMR spectroscopists do when they solve a structure," Mirny said.
Virnau is working on a computer program and a web server, soon to be publicly available, that can analyze the structure of any protein to see if it has knots, which he believes could be helpful to researchers in structural genomics. (Structural genomics aims to determine the structure of all proteins produced by a given organism.)
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.
They have also found examples of proteins that are closely related and structurally similar except for the presence or absence of a knot. Two versions of the enzyme transcarbamylase, from humans and certain bacteria, catalyze different reactions, depending on whether or not there is a knot. The researchers speculate that somewhere along the evolutionary line, the sequence that allowed a protein to form the knot was added or deleted.
The third author on the paper is Mehran Kardar, an MIT physics professor. The research was funded by the National Science Foundation and the German Research Foundation.