Abstract
Snake venom defensins are a toxin family found in rattlesnake venoms (Crotalus) 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 (C. durissus terrificus) and myotoxin a (C. viridis viridis), 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 in silico 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(v)1.3 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.