The T-knot motif revisited

The T-knot scaffold, a disulphide-reinforced structural motif shared by sev eral proteins with very different biological functions, has been defined as 'a stretch of the protein chain which comprises two strands of a beta-shee t and three loops, knotted by two disulphides into the shape of the letter T'. In this communication we show that the presence of a central beta-sheet is not a required structural feature for proteins sharing the T-knot topol ogy. Moreover, superposition of the three-dimensional structures of represe ntative members of the T-knot family highlights a common and structurally w ell-defined core, formed by the two knotted disulphides, substituting for a larger residue-based hydrophobic core. These results suggest that folding and stability of the T-knot scaffold mainly depend on the geometry of the t wo knotted disulphides and on the loop length, and that the secondary struc ture elements are not a prerequisite for motif formation. Accordingly, a re definition of the T-knot motif is proposed.