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.
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- Leulliot N, Bohnsack MT, Graille M, Tollervey D, Van Tilbeurgh H.(2008). The yeast ribosome synthesis factor Emg1 is a novel member of the superfamily of alpha/beta knot fold methyltransferases. Nucleic Acids Res 36(2):629-39.
- Tkaczuk KL, Dunin-Horkawicz S, Purta E, Bujnicki JM. (2007). Structural and evolutionary bioinformatics of the SPOUT superfamily of methyltransferases. BMC Bioinformatics. 8:73.
- Mallam AL, Jackson SE. (2006). Probing nature's knots: the folding pathway of a knotted homodimeric protein. J Mol Biol 359(5):1420-36.
- Khatib F, Weirauch MT, Rohl CA. (2006). Rapid knot detection and application to protein structure prediction. Bioinformatics 22(14):e252-9.
- Lai YL, Yen SC, Yu SH, Hwang JK (2007). pKNOT: the protein KNOT web server. Nucleic Acids Research 35:W420-424.