Cystine Knots

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The cystine knot structural motif is present in peptides and proteins from a variety of species, including fungi, okants, marine molluscs, insects and spiders. It comprises an embedded ring formed by two disulfide bonds and their connecting backbone segments which is threaded by a third disulfide bond. It is invariably associated with a nearby beta-sheet structure and appears to be a highly efficient motif for structure stabilization. Because of this stability, it makes an ideal framework for molecular engineering applications. Peptides containing this cystine knot are 26-48 residues long and include ion channel blockers, haemolytic agents as well as molecules having anitviral and antibacterial activities. The stability of peptide toxins containing the cystine knot motif, their range of bioactivities and their unique structural scaffold can be harnessed for molecular engineering applications and in drug design.

There are three classes of cystine knots: Growth Factor Cystine Knot (GFCK), Inhibitor Cystine Knot (ICK) and the Cyclic Cystine Knot (CCK). All are shown below.



Schematic diagrams of the three classes of cystine knot. The beta-strands are drawn as arrows, the cysteine residues are labelled I-VI in order from the N- to C-terminus and the disulfide bonds are represented as shaded lines. The penetrating disulfide bond for the growth factor cystine knot is Cys(I-IV) whereas it is Cys(III-VI) in the inhibitor cystine knot and cyclic cystine knot peptides.