Peptide Toxins from Marine Conus Snails with Activity on Potassium Channels and/or Currents

Abstract

Toxins from Conus snails are peptides characterized by a great structural and functional diversity. They have a high affinity for a wide range of membrane proteins such as ion channels, neurotransmitter transporters, and G protein-coupled receptors. Potassium ion channels are integral proteins of cell membranes that play vital roles in physiological processes in muscle and neuron cells, among others, and reports in the literature indicate that perturbation in their function (by mutations or ectopic expression) may result in the development and progression of different ailments in humans. This review aims to gather as much information as possible about Conus toxins (conotoxins) with an effect on potassium channels and/or currents, with a perspective of exploring the possibility of finding or developing a possible drug candidate from these toxins. The research indicates that, among the more than 900 species described for this genus, in only 14 species of the >100 studied to date have such toxins been found (classified according to the most specific evidence for each case), as follows: 17 toxins with activity on two groups of potassium channels (Kv and KCa), 4 toxins with activity on potassium currents, and 5 toxins that are thought to inhibit potassium channels by symptomatology and/or a high sequence similarity.

Keywords: conopeptides; conotoxins; voltage-gated potassium channels.

Figure 1

Comprehensive overview of potassium channel-targeting conotoxins and their structural/functional relationships. The figure uses a radial organization around a central Conus shell, presenting information in three concentric layers: Inner layer, names of the toxins. Middle layer, structural information: conotoxin structures are shown as ribbon diagrams; experimentally determined structures (Protein Data Bank) are displayed in the color scheme that appears in the thumbnail images of each toxin, while computational predictions (PEP-FOLD3) appear in gray. Outer layer, evidence classification: Target subtype (connecting lines indicate validated interactions with specific potassium channel targets; multiple connections highlight toxins with broad-spectrum activity), “By in vivo bioassays” (Toxins validated through functional studies), “By similarity” (candidate toxins identified through sequence homology analysis), or “By effect on potassium currents” (toxins with demonstrated electrophysiological effects).