Trefoil knot fold

From Wikipedia, the free encyclopedia

A deep trefoil knot in a Thermus thermophilus RNA methyltransferase domain (PDB ID 1IPA). The knotted C-terminus of the protein is shown in blue.

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 RNA binding proteins in archaea^[1] and in methyltransferase proteins^[2] and tRNA modification proteins^[3] in the bacterium Thermus thermophilus. Knotted proteins have not yet been reported in eukaryotes.

In many cases the trefoil knot is part of the active 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^[4]. 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^[5].

[edit] External links

[edit] References

^ Zarembinski TI, Kim Y, Peterson K, Christendat D, Dharamsi A, Arrowsmith CH, Edwards AM, Joachimiak A. (2003). Deep trefoil knot implicated in RNA binding found in an archaebacterial protein. Proteins 50(2):177-83.
^ Nureki O, Shirouzu M, Hashimoto K, Ishitani R, Terada T, Tamakoshi M, Oshima T, Chijimatsu M, Takio K, Vassylyev DG, Shibata T, Inoue Y, Kuramitsu S, Yokoyama S. (2002). An enzyme with a deep trefoil knot for the active-site architecture. Acta Crystallogr D Biol Crystallogr 58(Pt 7):1129-37.
^ Nureki O, Watanabe K, Fukai S, Ishii R, Endo Y, Hori H, Yokoyama S. (2004). Deep knot structure for construction of active site and cofactor binding site of tRNA modification enzyme. Structure 12(4):593-602.
^ 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.