Abstract

Plants have evolved with an array of proteins and peptides involved in defense against pests and pathogens. Cyclotides are a family of plant-derived head-to-tail cyclic mini-proteins of 28-37 amino acids, featuring three disulfide bridges forming a characteristic cyclic cystine knot (CCK) motif. This motif imbues the cyclotides with structural rigidity and remarkable stability to thermal, chemical and enzymatic degradation. Tolerance of CCK motif to sequence variation (other than Cys residues) has resulted in extensive sequence diversity and identification of cyclotides in various plant families. Their extensive sequence variation suggests that they have evolved to target a wide range of potential sites, although they still retain a well-conserved core sequence. Several different cyclotides occur in high abundance in aerial plant tissues like leaves and flowers of individual plants where their natural function is thought to be host defense as an insecticidal agent. In this work, we present a comprehensive phylogenetic analysis of known cyclotides from various plant families based on their distribution, precursor gene structure, post-translational processing mechanism and protein 3D structure. The results present an insight on understanding the evolution of this diverse family of cyclic defense proteins in plants.