Abstract:
We have isolated a novel family of insect-selective
neurotoxins that appear to be the most potent blockers
of insect voltage-gated calcium channels reported to
date. These toxins display exceptional phylogenetic
specificity, with at least a 10,OO0-fold preference for insect
versus vertebrate calcium channels. The structure
of one of the toxins reveals a highly structured, disulfide-
rich core and a structurally disordered C-terminal
extension that is essential for channel blocking activity.
Weak structural/functional homology with ω-agatoxin-
IVA/B, the prototypic inhibitor of vertebrate P-type calcium
channels, suggests that these two toxin families
might share a similar mechanism of action despite their
vastly different phylogenetic specificities.
