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 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. Moreover, protein engineering and synthetic biology has been recently applied for the design of this fold. Here you can see the crystal structure of a totally synthetic peptide that adopts the trefoil knot fold (PDB code: 7SQ4)
#molecularart ... #immolecular ... #syntheticbiology ... #engineering ... #peptide ... #trefoil ... #knot ... #folding ... #xray
Structure of the trefoil knot peptide rendered with @proteinimaging and depicted with @corelphotopaint
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. Moreover, protein engineering and synthetic biology has been recently applied for the design of this fold. Here you can see the crystal structure of a totally synthetic peptide that adopts the trefoil knot fold (PDB code: 7SQ4)
#molecularart ... #immolecular ... #syntheticbiology ... #engineering ... #peptide ... #trefoil ... #knot ... #folding ... #xray
Structure of the trefoil knot peptide rendered with @proteinimaging and depicted with @corelphotopaint
