Drosotoxin, a selective inhibitor of tetrodotoxin-resistant sodium channels

Venom evolution through gene duplications

“…In another example, Zhu et al (2010) showed through an ex vivo study that scorpion sodium channel inhibiting toxins may have originated from non-venom ancestral antifungal defensins by producing a chimeric recombinant that represented a possible evolutionary intermediate. This protein exhibited a reduced ability in inhibiting a broad spectrum of sodium channels compared with the toxin (Zhu et al, 2010).…”

“…This protein exhibited a reduced ability in inhibiting a broad spectrum of sodium channels compared with the toxin (Zhu et al, 2010).…”

NaVβ Subunits Modulate the Inhibition of NaV1.8 by the Analgesic Gating Modifier μO-Conotoxin MrVIB

“…The O-conotoxins are one of the few ligands known to block Na V 1.8 and TTX-resistant currents in mammalian DRG neurons (Daly et al, 2004;Bulaj et al, 2006;Ekberg et al, 2006), although the selection is being expanded (Zhu et al, 2010). Two members of the O family have been identified, MrVIA and MrVIB, which differ in only 3 of their 31 residues (Fainzilber et al, 1995;McIntosh et al, 1995).…”

Nematode-derived drosomycin-type antifungal peptides provide evidence for plant-to-ecdysozoan horizontal transfer of a disease resistance gene

“…Similarly, drosomycin has been found to gain ability in interacting with the fly voltage-gated sodium channel, possibly acting as a neuropeptide 25 . In C. remanei, cremycin-15 has evolved antibacterial activity described here, while scorpion venom-derived DTAFPs have switched their targets from fungi to animal sodium channels [24][25][26] . All these observations suggest that the gene can be fixed only in organisms where it developed important functions following gene duplication and speciation.…”

“…Experimental deletion of the NC-domain of a scorpion toxin resulted in antifungal ability of the toxin 25 , whereas the addition of the NC-domain of a toxin on the drosomycin scaffold led to a neurotoxin targeting rat sodium channels 26 . These data provide convincing functional evidence in favour of evolutionary link between drosomycins and scorpion sodium channel toxins, and present an example of divergent evolution occurring in a specific arthropod lineage, in which a DTAFP evolved into a neurotoxin [24][25][26] . The insertion of a small fragment, as the N-turn of the scorpion toxins, in the N-terminal region of a DTAFP is also seen in mehamycin (Fig.…”