Science, Technology and Engineering

Anderson Laboratory

Department of Biochemistry

Research - Plant Cyclotides

Naturally occurring circular proteins (i.e., proteins in which the N- and C- termini are linked via a peptide bond) were unknown before the mid 1990s; however, there have been increasing reports of both naturally occurring and synthetic circular proteins over the last few years. Of particular interest among naturally occurring examples have been a series of plant-derived proteins referred to as the cyclotides. The cyclotides comprise 29-31 amino acids, including six highly conserved Cys residues that form a cystine knot. In this structural motif, an embedded ring formed by two disulfide bonds and their connecting backbone segments is penetrated by a third disulfide bond. The combination of a cystine knot embedded in a cyclic backbone, referred to as a cyclic cystine knot, produces a unique protein fold that is topologically complex and has exceptional chemical and biological stability. 

The cyclotides contrast with the other circular proteins in that they have highly defined three-dimensional structures and, despite their small size, may be regarded as miniproteins. This attribute arises primarily from the knotted network of disulfide bonds that stabilizes the structures. The well-defined structures are associated with a range of biological activities. Indeed, the cyclotides were originally discovered either from screening programs or from anecdotal reports of their biological activity in traditional medicines. For example, in 1970, kalata B1 was reported as the active ingredient in a tea used by women in the Congo region of Africa to accelerate childbirth, although it was some 25 years later before the sequence and cyclic nature of the peptide were determined. The cyclotides display a diverse range of activities including anti-HIV, neurotensin binding and hemolytic activity, but their function in plants is not well understood. A role in plant defense against microorganisms and insects has been suggested.

We are interested in understanding the role of the protein in the plant and how it adopts its cyclic conformation.

Other research interests