ISSN 0006-2979, Biochemistry (Moscow), 2015, Vol. 80, No. 13, pp. 1764-1799. © Pleiades Publishing, Ltd., 2015. Original Russian Text © A. I. Kuzmenkov, E. V. Grishin, A. A. Vassilevski, 2015, published in Uspekhi Biologicheskoi Khimii, 2015, Vol. 55, pp. 289-350. REVIEW Diversity of Potassium Channel Ligands: Focus on Scorpion Toxins A. I. Kuzmenkov*, E. V. Grishin, and A. A. Vassilevski* Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia; E-mail:
[email protected];
[email protected] Received June 16, 2015 Revision received July 21, 2015 Abstract—Potassium (K+) channels are a widespread superfamily of integral membrane proteins that mediate selective transport of K+ ions through the cell membrane. They have been found in all living organisms from bacteria to higher mul- ticellular animals, including humans. Not surprisingly, K+ channels bind ligands of different nature, such as metal ions, low molecular mass compounds, venom-derived peptides, and antibodies. Functionally these substances can be K+ channel pore blockers or modulators. Representatives of the first group occlude the channel pore, like a cork in a bottle, while the second group of ligands alters the operation of channels without physically blocking the ion current. A rich source of K+ channel ligands is venom of different animals: snakes, sea anemones, cone snails, bees, spiders, and scorpions. More than a half of the known K+ channel ligands of polypeptide nature are scorpion toxins (KTx), all of which are pore blockers. These com- pounds have become an indispensable molecular tool for the study of K+ channel structure and function. A recent special interest is the possibility of toxin application as drugs to treat diseases involving K+ channels or related to their dysfunction (channelopathies).