A conserved cysteine framework of toxins from Viola tricolor and Conus brunneus characterized in the Drosophila melanogaster Giant Fiber System

Conotoxins are disulfide rich peptides present in the venom of cone snails, a genus of marine mollusks that prey upon fish, worms, and other mollusks. Conotoxins are promising drugs leads with great prospects in the treatment of diseases and disorders such as chronic pain, multiple sclerosis and Parkinson’s and Alzheimer’s diseases. Similar compounds can be found in plants; for example, cyclotides, which are cyclic peptides isolated from the Violaceae violet, Rubiaceae coffee, and Cucurbitaceae cucurbit families and they have a wide range of biological activities, such as anti-HIV, uterotonic, and antimicrobial. Cyclotides have a cyclic cysteine knot motif characterized by a cyclic backbone and six conserved cysteine residues that form the three disulfide bridges of the “knot”. This motif provides cyclotides with superior stability against thermal, chemical, and enzymatic degradation; marking them as potential frameworks for peptide drug delivery. Cysteine framework IX conotoxins C-C-C-CXC-C, isolated from the venom of Conus brunneus, contain the same cysteine framework, homologous sequences, and similar 3D structures to cyclotides. Presented are details on the isolation of these conotoxins and cyclotides, from Viola tricolor, and the characterization of their activity in the Drosophila melanogaster Giant Fiber System GFS, which contains GAP, acetylcholine, and glutamate synapses.