Snake venom defensins: Defining the structural and functional characteristics of the toxin family

Snake venom defensins are a toxin family found in rattlesnake venoms (<i>Crotalus</i>) which are comprised of crotamine-like peptides and myotoxins. Their tertiary structure resembles the β-defensin family structure. Toxins from this family, such as crotamine (<i>C. durissus terrificus</i>) and myotoxin a (<i>C. viridis viridis</i>), have been described to generate paralysis through K_v 1.3 channel blockade, using three functional basic-hydrophobic dyads (Y-K, R-W, and R-W). However, the structural and functional properties of other snake venom defensins are scarcely described. For that reason, we evaluated the structural-functional characteristics of the rattlesnake venom defensins on the K_v 1.3 channel through <i>in silico</i> analysis. 38 snake venom defensins were found to be peptides from 41 to 48 residues with a highly conserved sequence. The three-dimensional structures had great similitude (RMSD, <1.1 Å). Moreover, molecular dynamics simulations showed that the structures were stable (0.445 ± 0.23 nm). It was found that the snake venom defensins contain two or three basic-hydrophobic dyads, the first one is present in the N-terminal region of the defensin comprised by YK. The dyads two and three are contiguous, forming a motif in the γ-core, of which there are seven phenotypes: RWKW, RWRW, PWRR, PWKR, RWKR, RLGW, and GWRR. These dyads played a key role in the interaction of the defensins with the pore residues of the K_v1.3 channel. These results demonstrated that snake venom defensins have common structural and functional properties, interacting with the K_v 1.3 channel through the basic-hydrophobic dyads.