Α-Conotoxin

Alpha conotoxin precursor
1AKG.
Identifiers
Symbol Toxin_8
Pfam InterPro PROSITE PDOC60004
SCOP SUPERFAMILY OPM superfamily OPM protein 1akg
Omega conotoxin
1DW5.
Identifiers
Symbol Conotoxin
Pfam InterPro IPR004214
SCOP SUPERFAMILY OPM superfamily OPM protein 1fyg

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.[1] Over the last few decades conotoxins have been subject of pharmacological interest.[2]

Types and biological activities of conotoxins

The number of conotoxins whose activities have been determined so far is five, and they are called the α(alpha)-, δ(delta)-, κ(kappa)-, μ(mu)-, and ω(omega)- types. Each of the five types of conotoxins attacks a different target:

Disulfide connectivities

Types of conotoxins also differ in the number and pattern of disulfide bonds.[10] The disulfide bonding network, as well as specific amino acids in inter-cysteine loops, provide the specificity of conotoxins.[11]

Omega, delta and kappa conotoxins

Omega, delta and kappa families of conotoxins have a knottin or inhibitor cysteine 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.[10]

Mu conotoxins

Mu-conotoxin
nmr solution structure of piiia toxin, nmr, 20 structures
Identifiers
Symbol Mu-conotoxin
Pfam Pfam clan InterPro IPR008036
SCOP SUPERFAMILY OPM superfamily OPM protein 1ag7

Mu-conotoxins have two types of cysteine arrangements, but the knottin scaffold is not observed.[12] Mu-conotoxins target the muscle-specific voltage-gated sodium channels,[10] and are useful probes for investigating voltage-dependent sodium channels of excitable tissues.[12][13] Mu-conotoxins target the voltage-gated sodium channels, preferentially those of skeletal muscle,[14] and are useful probes for investigating voltage-dependent sodium channels of excitable tissues.[15]

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.[16]

Alpha conotoxins

Alpha conotoxins have two types of cysteine arrangements,[17] and are competitive nicotinic acetylcholine receptor antagonists.

See also

References

This article incorporates text from the IPR008036

External links

  • Medical Subject Headings (MeSH)

This article incorporates text from the IPR004214