InterPro: IPR004214 Conotoxin

Cone snail toxins, conotoxins, are small neurotoxic peptides with disulphide connectivity that target ion-channels or G-protein coupled receptors. Based on the number and pattern of disulphide bonds and biological activities, conotoxins can be classified into several families [1]. Omega, delta and kappa families of conotoxins have a knottin or inhibitor cysteine knot scaffold. The knottin scaffold is a very special disulphide-through-disulphide knot, in which the III-VI disulphide bond crosses the macrocycle formed by two other disulphide 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 disulphide bonding network, as well as specific amino acids in inter-cysteine loops, provide the specificity of conotoxins [2]. 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 [1]. Mu conotoxins have two types of cysteine arrangements, but the knottin scaffold is not observed. Mu conotoxins target the voltage-gated sodium channels [1], and are useful probes for investigating voltage-dependent sodium channels of excitable tissues [3]. Alpha conotoxins have two types of cysteine arrangements [4], and are competitive nicotinic acetylcholine receptor antagonists.