Grandal, Meghan, et al. “Proteogenomic Assessment of Intraspecific Venom Variability: Molecular Adaptations in the Venom Arsenal of Conus Purpurascens.” Molecular & Cellular Proteomics, Elsevier BV, May 2021, p. 100100. Crossref, doi:10.1016/j.mcpro.2021.100100.
Cone snails produce venom that contains diverse groups of peptides (conopeptides/conotoxins) and display a wide mass range, high rate of post-translational modifications, and many potential pharmacological targets. Here we employ a proteogenomic approach to maximize conopeptide identification from the injected venom of Conus purpurascens. mRNA sequences from C. purpurascens venom ducts were assembled into a search database and complemented with known sequences and de novo approaches. We used a top-down peptidomic approach and MS/MS identification to compare injected venom samples of 27 specimens. This intraspecific analysis yielded 543 unique conopeptide identifications, which included 33 base conopeptides and their toxiforms, 21 of which are novel. The results reveal two distinct venom profiles with different synergistic interactions to effectively target neural pathways aimed to immobilize prey. These venom expression patterns will aid target prediction, a significant step towards developing conotoxins into valuable drugs or neural probes.