Novel O‐superfamily Conotoxins Identified by cDNA Cloning From Three Vermivorous Conus Species

Abstract

The O‐superfamily of conotoxins includes several subfamilies with different pharmacological targets, all of which are voltage‐gated ion channels and distributed widely in varied Conus species. The venom components from any Conus species are quite distinct from those of other species. Seven novel O‐superfamily peptides were identified by cDNA cloning from the three vermivorous Conus species of C. betulinus, C. lividus and C. caracteristicus native to Hainan. They share three common signal sequences, and a conserved arrangement of cysteine residues (C–C–CC–C–C). Phylogenetic analysis of newly found conotoxins in this study and known homologue O‐superfamily sequences from the other Conus species was performed systematically. Divergence and percentage identity of the amino acid sequences of the signal regions suggest that the novel conotoxins described in this investigation belong to the three broad clades: MSGL, ME‐QK and MKLT, each of which has its own characteristic signature signal sequence and cysteine codon conservation. Relative to this work, it is noted that O‐superfamily conotoxins are not well represented from vermivorous species. The elucidated cDNAs of these newly found vermivorous toxins would facilitate a better understanding for basic research and drug discovery.

Atypical α-Conotoxin LtIA from Conus litteratus Targets a Novel Microsite of the α3β2 Nicotinic Receptor

“…Over the past several years, these "conotoxins" have been shown to have a remarkable diversity of pharmacological function and utility (7,8). Based on molecular structure, the conotoxins have been grouped into A, O, M, P, R, S, and T superfamilies (9,10). A subgroup of compounds found within the A superfamily is the ␣-conotoxins.…”

Embryonic Toxin Expression in the Cone Snail Conus victoriae

“…O-superfamily toxins exhibit a characteristic pattern of 6 cysteines (C-C-CC-C-C) that form three disulfide bonds. Members of this family are known modulators of voltage-sensitive calcium, potassium, and sodium channels (44,46). Alignment of the novel O-conotoxins with other members of the O-superfamily revealed high sequence similarity to the O2 gene superfamily (Fig.…”

“…Alignment of the novel O-conotoxins with other members of the O-superfamily revealed high sequence similarity to the O2 gene superfamily (Fig. 2B), peptides with an as yet unidentified target receptor (44,47).…”

Glycine-rich conotoxins from the Virgiconus clade

“…Each conotoxin superfamily can be further subdivided into pharmacological families (Terlau and Olivera, 2004). For example, the O1-conotoxin superfamily comprises the ω-conotoxins, which target voltage-gated calcium channels (Hillyard et al, 1992; Olivera et al, 1985; Zhangsun et al, 2006), the κ-conotoxins, which target voltage-gated potassium channels (Shon et al, 1998; Terlau et al, 1996) and the δ-and the µO-conotoxin families, which target voltage-gated sodium channels at different sites (Leipold et al, 2005; McIntosh et al, 1995; Shon et al, 1995; Terlau et al, 1996; Wilson et al, 2015). …”