Trefoil knot fold

The trefoil knot fold is a protein fold in which the protein backbone is twisted into a trefoil knot shape. "Shallow" knots in which the tail of the polypeptide chain only passes through a loop by a few residues are uncommon, but "deep" knots in which many residues are passed through the loop are extremely rare. Deep trefoil knots have been found in the SPOUT superfamily including methyltransferase proteins involved in posttranscriptional RNA modification in all three Domains of Life, including bacterium Thermus thermophilus  and  proteins, in archaea and in eukaryota.

In many cases the trefoil knot is part of the active site or a ligand-binding site and is critical to the activity of the enzyme in which it appears. Before the discovery of the first knotted protein, it was believed that the process of protein folding could not efficiently produce deep knots in protein backbones. Studies of the folding kinetics of a dimeric protein from Haemophilus influenzae have revealed that the folding of trefoil knot proteins may depend on proline isomerization. Computational algorithms have been developed to identify knotted protein structures, both to canvas the Protein Data Bank for previously undetected natural knots and to identify knots in protein structure predictions, where they are unlikely to accurately reproduce the native-state structure due to the rarity of knots in known proteins. Currently, there is a web server pKNOT available to detect knots in proteins as well as to provide information on knotted proteins in Protein Data Bank.