8.B.35.  The Conantokin (Conantokin) Family 

Conus venoms contain a diversity of pharmacologically active small peptides. Their targets are ion channels and receptors in the neuromuscular system. The venom of Conus geographus contains high-affinity peptides that act on voltage-sensitive calcium channels, sodium channels, N-methyl-D-aspartate (NMDA) receptors, acetylcholine receptors, and vasopressin receptors; many more peptides with still uncharacterized receptor targets are present in this venom. It seems that the Conus species (approximately 500 known) will each use a distinctive assortment of peptides and that the pharmacological diversity in Conus venoms may be comparable to that of plant alkaloids or secondary metabolites of microorganisms. The cone snails may generate this diverse spectrum of venom peptides by a "fold-lock-cut" synthetic pathway. These peptides are specific enough to discriminate effectively between closely related receptor subtypes and can be used for structure-function correlations (Olivera et al. 1990).


 

References:

Liu, Z., H. Li, N. Liu, C. Wu, J. Jiang, J. Yue, Y. Jing, and Q. Dai. (2012). Diversity and evolution of conotoxins in Conus virgo, Conus eburneus, Conus imperialis and Conus marmoreus from the South China Sea. Toxicon 60: 982-989.

Olivera, B.M., J. Rivier, C. Clark, C.A. Ramilo, G.P. Corpuz, F.C. Abogadie, E.E. Mena, S.R. Woodward, D.R. Hillyard, and L.J. Cruz. (1990). Diversity of Conus neuropeptides. Science 249: 257-263.

Examples:

TC#NameOrganismal TypeExample
8.B.35.1.1

Conantokin-G of 100 aas and 1 N-terminal TMS.  Conantokins inhibit N-methyl-D-aspartate (NMDA) receptors. This toxin is selective for the NR2B/GRIN2B subunit. It induces sleep-like symptoms in young mice and hyperactivity in older mice (Olivera et al. 1990).

Conantokin-G of Conus geographus (Geography cone) (Nubecula geographus)

 
8.B.35.1.2

Eb-conantokin-like proteinof 100 aas and 1 N-terminal TMS (Liu et al. 2012).

Conantokin of Conus eburneus

 
8.B.35.1.3

Conotoxin of 117 aas and 1 N-terminal TMS.

Conotoxin of Conus betulinus

 
Examples:

TC#NameOrganismal TypeExample
8.B.35.2.1

Uncharacterized protein of 182 aas and 2 putative TMSs.  Homoogy with 8.B.35.1 proteins has not been established, but sequence similarity in the first 81 aas has been observed.

UP of Marinobacter aromaticivorans