Conotoxin

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title: "Conotoxin" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["snail-toxins", "ion-channel-toxins", "neurotoxins", "nicotinic-antagonists", "peripheral-membrane-proteins", "cysteine-rich-proteins"] description: "Group of neurotoxins" topic_path: "general/snail-toxins" source: "https://en.wikipedia.org/wiki/Conotoxin" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Group of neurotoxins ::

::data[format=table title="Infobox protein family"]

Field	Value
Symbol	Toxin_8
Name	Alpha conotoxin precursor
image	alpha-Conotoxin from Conus pennaceus 1AKG.png
caption	α-Conotoxin PnIB from C. pennaceus, disulfide bonds shown in yellow. From the University of Michigan's Orientations of Proteins in Membranes database, .
Pfam	PF07365
InterPro	IPR009958
PROSITE	PDOC60004
SCOP	1mii
OPM family	148
OPM protein	1akg
::

| Symbol = Toxin_8 | Name = Alpha conotoxin precursor | image = alpha-Conotoxin from Conus pennaceus 1AKG.png | width = | caption = α-Conotoxin PnIB from C. pennaceus, disulfide bonds shown in yellow. From the University of Michigan's Orientations of Proteins in Membranes database, . | Pfam= PF07365 | InterPro= IPR009958 | SMART= | PROSITE = PDOC60004 | SCOP = 1mii | TCDB = | OPM family = 148 | OPM protein = 1akg | PDB = | Symbol = Conotoxin | Name = Omega conotoxin | image =Ziconotide 1DW5.png | width = | caption =Schematic diagram of the three-dimensional structure of ω-conotoxin MVIIA (ziconotide). Disulfide bonds are shown in gold. From . | Pfam= PF02950 | InterPro= IPR004214 | SMART= | PROSITE = | SCOP = 2cco | TCDB = | OPM family= 112 | OPM protein= 1fyg | PDB= A conotoxin is one of a group of neurotoxic peptides isolated from the venom of the marine cone snail, genus Conus.

Conotoxins, which are peptides consisting of 10 to 30 amino acid residues, typically have one or more disulfide bonds. Conotoxins have a variety of mechanisms of actions, most of which have not been determined. However, it appears that many of these peptides modulate the activity of ion channels. Over the last few decades conotoxins have been the subject of pharmacological interest.

The LD50 of conotoxin ranges from 5-25 μg/kg.

Hypervariability

Conotoxins are hypervariable even within the same species. They do not act within a body where they are produced (endogenously) but act on other organisms. Therefore, conotoxin genes experience less selection against mutations (like gene duplication and nonsynonymous substitution), and mutations remain in the genome longer, allowing more time for potentially beneficial novel functions to arise. Variability in conotoxin components reduces the likelihood that prey organisms will develop resistance; thus cone snails are under constant selective pressure to maintain polymorphism in these genes because failing to evolve and adapt will lead to extinction (Red Queen hypothesis).

Disulfide connectivities

Types of conotoxins also differ in the number and pattern of disulfide bonds. The disulfide bonding network, as well as specific amino acids in inter-cysteine loops, provide the specificity of conotoxins.

Types and biological activities

As of 2005, five biologically active conotoxins have been identified. Each of the five conotoxins attacks a different target:

• α-conotoxin inhibits nicotinic acetylcholine receptors at nerves and muscles.
• δ-conotoxin inhibits fast inactivation of voltage-dependent sodium channels.
• κ-conotoxin inhibits potassium channels.
• μ-conotoxin inhibits voltage-dependent sodium channels in muscles.
• ω-conotoxin inhibits N-type voltage-dependent calcium channels. Because N-type voltage-dependent calcium channels are related to algesia (sensitivity to pain) in the nervous system, ω-conotoxin has an analgesic effect: the effect of ω-conotoxin M VII A is 100 to 1000 times that of morphine. Therefore, a synthetic version of ω-conotoxin M VII A has found application as an analgesic drug ziconotide (Prialt).

Alpha

Alpha conotoxins have two types of cysteine arrangements, and are competitive nicotinic acetylcholine receptor antagonists.

Delta, kappa, and omega

Omega, delta and kappa families of conotoxins have a knottin or inhibitor cystine knot scaffold. The knottin scaffold is a very special disulfide-through-disulfide knot, in which the III-VI disulfide bond crosses the macrocycle formed by two other disulfide bonds (I-IV and II-V) and the interconnecting backbone segments, where I-VI indicates the six cysteine residues starting from the N-terminus. The cysteine arrangements are the same for omega, delta and kappa families, even though omega conotoxins are calcium channel blockers, whereas delta conotoxins delay the inactivation of sodium channels, and kappa conotoxins are potassium channel blockers.

Mu

| Symbol = Mu-conotoxin | Name = Mu-conotoxin | image = PDB 1r9i EBI.jpg | width = | caption = nmr solution structure of piiia toxin, nmr, 20 structures | Pfam = PF05374 | Pfam_clan = CL0083 | InterPro = IPR008036 | SMART = | PROSITE = | MEROPS = | SCOP = 1gib | TCDB = | OPM family = 112 | OPM protein = 1ag7 | CAZy = | CDD = Mu-conotoxins have two types of cysteine arrangements, but the knottin scaffold is not observed. Mu-conotoxins target the muscle-specific voltage-gated sodium channels, and are useful probes for investigating voltage-dependent sodium channels of excitable tissues. Mu-conotoxins target the voltage-gated sodium channels, preferentially those of skeletal muscle, and are useful probes for investigating voltage-dependent sodium channels of excitable tissues.

Different subtypes of voltage-gated sodium channels are found in different tissues in mammals, e.g., in muscle and brain, and studies have been carried out to determine the sensitivity and specificity of the mu-conotoxins for the different isoforms.

References

References

1. (2004). "Conus venoms: a rich source of novel ion channel-targeted peptides". Physiol. Rev..
2. (2007). "Diversity of the neurotoxic Conus peptides: a model for concerted pharmacological discovery.". Molecular Interventions.
3. "Archived copy".
4. "Biological Agent Reference Sheet - Conotoxin". Emory University.
5. "toxin ld50 list".
6. (September 2012). "Adaptive radiation of venomous marine snail lineages and the accelerated evolution of venom peptide genes". Ann. N. Y. Acad. Sci..
7. (March 2012). "Venom evolution through gene duplications". Gene.
8. (July 2011). "Red Queen: from populations to taxa and communities". Trends Ecol. Evol..
9. (2001). "Cone venom--from accidental stings to deliberate injection". Toxicon.
10. (2000). "lambda-conotoxins, a new family of conotoxins with unique disulfide pattern and protein folding. Isolation and characterization from the venom of Conus marmoreus". J. Biol. Chem..
11. (2004). "Alpha-conotoxins as tools for the elucidation of structure and function of neuronal nicotinic acetylcholine receptor subtypes". Eur. J. Biochem..
12. (2005). "Molecular interaction of delta-conotoxins with voltage-gated sodium channels". FEBS Lett..
13. (1998). "kappa-Conotoxin PVIIA is a peptide inhibiting the shaker K+ channel". J. Biol. Chem..
14. (2004). "Using the deadly mu-conotoxins as probes of voltage-gated sodium channels". Toxicon.
15. (2000). "Structure-activity relationships of omega-conotoxins at N-type voltage-sensitive calcium channels". J. Mol. Recognit..
16. (1998). "Pharmacotherapeutic potential of omega-conotoxin MVIIA (SNX-111), an N-type neuronal calcium channel blocker found in the venom of Conus magus". Toxicon.
17. Prommer E. (2006). "Ziconotide: a new option for refractory pain". Drugs Today.
18. (1992). "Novel alpha- and omega-conotoxins from Conus striatus venom". Biochemistry.
19. (July 2002). "Solution structure of mu-conotoxin PIIIA, a preferential inhibitor of persistent tetrodotoxin-sensitive sodium channels". J. Biol. Chem..
20. (1985). "Conus geographus toxins that discriminate between neuronal and muscle sodium channels". J. Biol. Chem..
21. (August 1985). "Conus geographus toxins that discriminate between neuronal and muscle sodium channels". J. Biol. Chem..
22. Floresca CZ. (2003). "A comparison of the mu-conotoxins by [3H]saxitoxin binding assays in neuronal and skeletal muscle sodium channel.". Toxicol Appl Pharmacol.

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