Unveiling Venom: Comparison of Novel Conus tulipa Conotoxins to Other Species of Fish-Hunting Cone Snails

Abstract

Fish-hunting cone snails (genus Conus ) inject venom into their prey to cause paralysis. Conus venom is composed of different classes of peptides that are highly post-translationally modified. In this study, we look at the A-superfamily conotoxins, which includes α-conotoxins and αA-conotoxins that cause flaccid paralysis by inhibiting nicotinic acetylcholine receptors, and neuroexcitatory peptides that cause tetanic paralysis by an unknown mechanism. Neuroexcitatory peptides have only been discovered in fish-hunting Conus species, but not in a clade of fish-hunters that includes Conus tulipa . We identified eight novel α-conotoxins with multiple clones but no neuroexcitatory peptides in C. tulipa. A list of mass predictions was generated from the novel sequences accounting for all possible post-translational modifications in order to perform a mass match analysis with venom peptides using mass spectrometry. We also defined three novel subfamilies of α4/7 conotoxins in C. tulipa . The diversity of α4/7?s observed in C. tulipa warrants further investigation. Previous studies have shown that α4/7?s target a variety of neuronal-type nicotinic acetylcholine receptor subtypes, which could provide insight into the physiological roles of these receptor subtypes in pain, inflammation, nicotine addiction, Alzheimer?s disease, and Parkinson?s disease. We hope to continue our search for neuroexcitatory peptides in C. tulipa and extend that search to C. purpurascens of another fish-hunting clade. If we are successful, together with neuroexcitatory peptides from C. catus and C. striatus , we can test them on a zebrafish assay developed by my lab to perform a comparative study on venom peptide effects from different fish-hunting groups.