Inhibitor cystine knot

An inhibitor cystine knot (also known as ICK or Knottin) is a protein structural motif containing three disulfide bridges.

[3] Cystine knot motifs are found frequently in nature in a plethora of plants, animals, and fungi and serve diverse functions from appetite suppression to anti-fungal activity.

[6] CK peptide components of venoms target voltage-gated ion channels but members of the family also act as antibacterial and haemolytic agents.

The motif is similar to the cyclic cystine knot or cyclotide, but lacks the cyclisation of the polypeptide backbone which is present in the latter family.

The growth factor cystine knot (GFCK) is similar to the ICK but its topology is such that it is the bond between the first and fourth disulfide which threads through the loop.

Top: general schematic of the structure of a knottin. A macrocyclic knot is formed by the core of beta strands (arrows) and disulfide bonds (yellow connections between numbered cysteines). Knottins are differentiated from GFCKs by the connectivity of their cysteines. Bottom: The general structure is easily seen in this crystal structure of EETI II taken from the protein database (PDB: 2IT7).
MCh-1: A plant inhibitor cystine knot peptide from Momordica charantia . PDB entry 2m2q . [ 1 ]