Dipole moments of scorpion toxins direct the interaction towards small- or large-conductance Ca2+-activated K+ channels

Summary Ca²⁺-activated K⁺ channels consist of a large family of membrane proteins, among which two groups have been characterized by electrophysiological criteria, the small conductance (SK) and the large conductance (BK) Ca²⁺-activated K⁺ channels. Scorpion toxins that block K⁺ channels exhibit a common three-dimensional structure constituted of a short α-helix connected by disulfide bonds to a β-sheet. The leiurotoxin I (LTX1) related toxins interact specifically with the SK channel via basic residues of their α-helix, while the charybdotoxin (ChTX) family recognizes the BK channel with basic residues of their β-sheet. In an attempt to better understand the structure-activity relationships of these toxins and the characteristics of the electrostatic interactions with the receptor site, we investigated the electrostatic potential supported by natural toxins and a synthetic analogue to find out if it may help in understanding the molecular mechanisms involved in this peptide-protein interaction.