Identification of a novel S-superfamily conotoxin from vermivorous Conus caracteristicus

Conotoxins have been classified into several different superfamilies based on the highly conserved signal peptide sequences of their precursors. However, little is known about the five disulfide bonds containing S-superfamily conotoxins. Only two S-superfamily conotoxins have been identified but their cDNAs are not reported. In this work, we identified a novel S-superfamily conotoxin ca8a from vermivorous Conus caracteristicus. Its sequence shares no homology with those of two other previously reported toxins of the same superfamily, but they have the same cysteine framework, in particular the CX3CXC-CXC-CXCXC pattern at the C-terminal part. This implies that these toxins might have the same spatial scaffold, but different local conformation or residue side chains may be the cause of their different biological functions. Furthermore, the cDNA of ca8a was cloned with the RACE method. ca8a has a signal peptide sequence different from those of other conotoxins. This gives a defining feature of S-superfamily conotoxins and led to the cloning of more S-superfamily conotoxins from cone snails of different prey types, which indicates that S-superfamily conotoxins widely exist. These results will certainly enrich our understanding of the highly diversified S-superfamily conotoxins.