Conus geographus Conotoxins

In the fish-hunting cone snail venoms, a- and w-conotoxins are ubiquitously distributed. As noted above, z-conotoxins have only been found in one species. Conus geographus. In addition to these three well-characterized classes, however, a fourth class of paralytic conotoxins has been found. In contrast to the a-, z-, and... 

Another potentially paralytic conotoxin was recently described this was a peptide purified from Conus geographus venom, which like / -conotoxin appeared to target to voltage-sensitive Na channels. However, the structure of "conotoxin GS" [nomenclature of Yanagawa et al. (J7)] was less homologous to / -conotoxins than to the w-conotoxins, which are Ca channel blockers. The same peptide was purified and characterized using a different assay, the induction of highly aberrant behavior upon ic injection of mice (L. J. Cruz, unpublished data). 

Conotoxins are small (10-30 amino acids), disulphide-rich, conformationally constrained peptides produced by marine mollusks such as cone snails. The fish-hunting snails, in particular Conus geographus, have been extensively studied. Depending upon the arrangement of disulphide bonds and the number of residues between cysteines, five or more classes of conotoxin can be structurally identified ... 

Olivera BM, McIntosh JM, Cruz LJ, Luque FA, Gray WR (1984) Purification and sequence of a presynaptic peptide toxin from Conus geographus venom. Biochemistry 23 5087-90 Olivera BM, Miljanich GP, Ramachandran J, Adams ME (1994) Calcium channel diversity and neurotransmitter release the omega-conotoxins and omega-agatoxins. Annu Rev Biochem 63 823-67... 

FIGU RE 5.1 Upper panel shows the sequence of CO-conotoxins isolated from Conus geographus (GVIA), Conus magus (MVllA, MVllC, and MVllD) and Conus Striatus (SVIA). Lower panel shows the arrangement of the cys residues that constitutes the four-loop structure. 

Between 6 and 10 homologous peptides have been extensively characterized for each toxin class. Although uj- and a-conotoxins have been isolated from several fish-hunting Conus species, x-conotoxins have so far been isolated only from C. geographus venom. 

As indicated, co-conotoxins are found in almost aU fish-hunting Conus species examined up to now. The most thoroughly studied are the venoms from C. geographus, C. magus, and C. striatus. Several of these peptides have been purified, sequenced, and synthesized (with similar potency as the natural toxins) and they have become important tools for the identification and characterization of the different subtypes of voltage-dependent Ca channels found in neuronal tissues. 

With the exception of a-conotoxin SII from Conus striatus, all a-conotoxins have the cysteine pattern, CC—C—C (Myers et al., 1993) (see Table 4). Peptides from the fish-hunting species, C geographus, C. striatus and C. magus, have the consensus core sequence CC(N/H)PACGXX(Y/F)XC and two disulfide bonds that connect Cys to Cys and Cys to Cys. Comparison with the a-conotoxins recently isolated from C. pennaceus, a mollusc-hunter, and C. imperialism a worm-hunter, indicates variations in the size of the intercysteine loops. The second loop has seven amino acid residues in a-conotoxins PnIA and PnIB from C pennaceus (Fainzilber et al., 1994), and only three residues in a-conotoxin Iml from C. imperialis (McIntosh et al., 1994), compared to five residues in the other a-conotoxins. 

---