A cystine knot is a protein structural motif containing three disulfide bridges. The sections of polypeptide that occur between two of them form a loop through which a third disulfide bond passes, forming a rotaxane substructure. The cystine knot motif stabilizes protein structure and is conserved in proteins across various species. There are three types of cystine knot, which differ in the topology of the disulfide bonds:
The presence of the cyclic cystine knot motif was discovered when cyclotides were isolated from various plant families. The CCK motif has a cyclic backbone, triple stranded beta sheet, and cystine knot conformation. There are currently novel proteins being added to the cystine knot motif family, which are called the C-terminal cystine knot proteins. They share approximately 90 amino acid residues in their cysteine-rich C terminal regions. Inhibitor cystine knot is a structural motif with a triple stranded antiparallel beta sheet linked by three disulfide bonds, forming a knotted core. ICK motif can be found under the category of phylum, such as animals and plants. It is usually found in many venom peptides, which is in the venoms of snails, spiders, and scorpions. Peptide K-PVIIA that contains an ICK can undergo a successful enzymatic backbone cyclization. The disulfide connectivity and the common sequence pattern of ICK motif provide the stability of the peptides that supports cyclization.
The stability and structure of the cytosine knot motif implicates possible applications in drug design. The hydrogen bonding interactions between the disulfide bonds of the motif and beta-sheet structures gives rise to highly efficient structure stabilization. In addition, the size of the motif is approximately 30 amino acid residues. These two characteristics make it an attractive biomolecule to be used for drug delivery as it exhibits thermal stability, chemical stability, and proteolytic resistance. The biological activities of these molecules are partially due to Its unique interlocking arrangement and cyclized peptide backbone which contains a conserved sequence shared among circulins. Circulins have previously been identified in a screen for anti-HIV activity. Studies have shown that cystine knot proteins can be incubated at temperatures of 65C or placed in 1N HCl/1N NaOH without loss of structural and functional integrity. Its resistance from oral and some intestinal proteases suggest possible use for oral delivery. Possible future applications that are being explored include pain relief as well as antiviral and antibacterial functions.
