Abstract
The cone snails (family Conidae) are the best known and most intensively studied venomous marine gastropods. However, of the total biodiversity of venomous marine mollusks (superfamily Conoidea, >20,000 species), cone snails comprise a minor fraction. The venoms of the family Drilliidae, a highly diversified family in Conoidea, have not previously been investigated. In this report, we provide the first biochemical characterization of a component in a Drilliidae venom and define a gene superfamily of venom peptides. A bioactive peptide, cdg14a, was purified from the venom of Clavus davidgilmouri Fedosov and Puillandre, 2020. The peptide is small (23 amino acids), disulfide-rich (4 cysteine residues) and belongs to the J-like drillipeptide gene superfamily. Other members of this superfamily share a conserved signal sequence and the same arrangement of cysteine residues in their predicted mature peptide sequences. The cdg14a peptide was chemically synthesized in its bioactive form. It elicited scratching and hyperactivity, followed by a paw-thumping phenotype in mice. Using the Constellation Pharmacology platform, the cdg14a drillipeptide was shown to cause increased excitability in a majority of non-peptidergic nociceptors, but did not affect other subclasses of dorsal root ganglion (DRG) neurons. This suggests that the cdg14a drillipeptide may be blocking a specific molecular isoform of potassium channels. The potency and selectivity of this biochemically characterized drillipeptide suggest that the venoms of the Drilliidae are a rich source of novel and selective ligands for ion channels and other important signaling molecules in the nervous system.
Highlights
Toxins 2020, 12, x FOR PEER REVIEWThe successful evolutionary radiation of the venomous marine snails in the superfamily Conoidea has generated a significant fraction of the biodiversity of living mollusks (>20,000 species) [1,2].Traditionally, three groups of gastropods, the cone snails, the auger snails, and the turrids, were thoughtThe successful evolutionary radiation of the venomous marine snails in the superfamily to comprise this superfamily
Sensu lato) comprise several revealed that while cone snails belong to a single monophyletic lineage, phylogenetically unrelated groups, some of which are more closely related to the cone snails than to and the auger snails can be grouped into a single clade, the conoidean have generally been referred to as turrids
The chromatographic profile of the crude venom is shown in Figure 2A; bioactivity was fraction indicated by the arrow in Figure 2A and 2B
Summary
The successful evolutionary radiation of the venomous marine snails in the superfamily Conoidea has generated a significant fraction of the biodiversity of living mollusks (>20,000 species) [1,2]. One of the most diverse phylogenetic lineages of former “turrids” whose most recent emendations [6], the members of the old family Turridae have been reclassified into 15 distinctiveness has long since been acknowledged, is the family Drilliidae [1,6]. One of the most diverse phylogenetic lineages of former “turrids” whose species-rich conoidean family remained uncharacterized, likely because distinctiveness has long sinceuntil beenrecently acknowledged, is thecompletely family Drilliidae [1,6] The venoms of this most species-rich drilliids areconoidean relativelyfamily small, until uncommon, and predominantly collected offshore. Clavus unizonalis, and Clavus suduirauti [9,10,11]
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