The T-knot motif revisited.
The T-knot scaffold, a disulphide-reinforced structural motif shared by several proteins with very different biological functions, has been defined as 'a stretch of the protein chain which comprises two strands of a beta-sheet 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 topology. Moreover, superposition of the three-dimensional structures of representative members of the T-knot family highlights a common and structurally well-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 two knotted disulphides and on the loop length, and that the secondary structure elements are not a prerequisite for motif formation. Accordingly, a redefinition of the T-knot motif is proposed.
Polticelli
F
F
Department of Biology, University of Rome "Tre", Italy.
Pascarella
S
S
Bordo
D
D
Bolognesi
M
M
Ascenzi
P
P
D000595:Amino Acid Sequence; D000925:Anticoagulants / Q000737:chemistry; D004220:Disulfides; D004815:Epidermal Growth Factor / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000737:chemistry; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013111:Spider Venoms / Q000737:chemistry
D000925:Anticoagulants; D004220:Disulfides; D008978:Mollusk Venoms; D011506:Proteins; D013111:Spider Venoms; D004815:Epidermal Growth Factor