Use of venom peptides to probe ion channel structure and function

Abstract

Venoms of snakes, scorpions, spiders, insects, sea anemones, and cone snails are complex mixtures of mostly peptides and small proteins that have evolved for prey capture and/or defense. These deadly animals have long fascinated scientists and the public. Early studies isolated lethal components in the search for cures and understanding of their mechanisms of action. Ion channels have emerged as targets for many venom peptides, providing researchers highly selective and potent molecular probes that have proved invaluable in unraveling ion channel structure and function. This minireview highlights molecular details of their toxin-receptor interactions and opportunities for development of peptide therapeutics.

FIGURE 1.

Venom peptides in complex with K⁺ and Na⁺ channels. Interacting residues are shown in stick representation, with toxins in red and the two apposing receptor subunits in blue and green. Except for the kaliotoxin-KcsA-K_v1.3 complex (14), derived from solid-state NMR data, all other toxin-receptor complexes are theoretical models derived from computational simulations. A, scorpion, anemone, and cone snail toxin complexes with their respective K⁺ channels. For clarity, only the turret selectivity filter of the channel is shown for BgK-K_v1.1 (16), PVIIA-Shaker (21), RIIIK-TSha1 (87), pl14a-K_v1.6 (88), and natrin-K_v1.3 (89) complexes. B, cone snail and scorpion toxin complexes with Na⁺ channels. μ-Conotoxin GIIIA (Ctx-GIIIA) is shown docked onto the selectivity filter of a Na_v1.4 model (90), and scorpion toxin CssIV is shown interacting with the voltage sensor of Na_v1.2 (33).