An Insect‐Specific Toxin from Centruroides noxius Hoffmann

Abstract

Scorpion toxins acting on sodium channels differ in their specificity. Toxic peptides specific towards mammals and arthropods (insects and/or crustaceans) have been described. Because of the similar three-dimensional fold of these peptides, the molecular base of their specificity is thought to reside in certain differences at the level of amino acid residues especially within or near the binding site of the toxin to the particular ion channel. The cDNA, amino acid sequence and biological activity of an insect-specific toxin, Cn10, from the scorpion Centruroides noxius Hoffmann is reported. The electrostatic potential surface around a three-dimensional model of Cn10 was calculated. It revealed that residues Tyr4, Lys13, Ile18, Leu19, Gly20, Lys43, Leu44, Thr57, Tyr58, Pro59, Thr64 and Cys65, situated at the side of the toxin proposed in the literature to bind to the sodium channel, constitute a positive surface region. Therefore, they may form the site that binds to the channel. Cn10 was included in a comparative analysis of two groups of natural variants, highly similar peptides of the genus Centruroides with specificities towards mammals or arthropods. A number of surface-accessible residues, consistently different between the two groups and situated near the putative binding site, may be of importance for the specificity of the analyzed toxins.

Dissection of the Functional Surface of an Anti-insect Excitatory Toxin Illuminates a Putative “Hot Spot” Common to All Scorpion β-Toxins Affecting Na+ Channels

“…3, A and B). In contrast to previous suggestions that positively charged residues have a mandatory role in the activity of scorpion ␤-toxins (19,36,37), the only positively charged residue with a functional role in Bj-xtrIT is His 25 . Because His 25 is not conserved in excitatory toxins or other ␤-toxins (Fig.…”

Are ticks venomous animals?

“…These venomous toxins have diversified their amino acid sequence causing a positive net charge on the all-atom Kunitz landscape (see Figure 2A). Reports have shown that toxins possessing a positive surface are most likely to target ion channels [84]. …”

NMR solution structure of Cn12, a novel peptide from the Mexican scorpion Centruroides noxius with a typical β‐toxin sequence but with α‐like physiological activity

“…Previous studies conducted with both a and b Na-ScTxs showed that small differences such as single amino-acid modifications or deletion of short stretches of sequence were enough to cause a dramatic change in toxicity to mice [53,54]. In recent years, many publications have contributed novel data and identified possible residues directly involved in the recognition and binding to Na + channels [4,5,18,33,[55][56][57][58][59][60][61][62][63][64][65]. However, a structural and functional characteristic unique to all ScTXs and Na + channels has not been found.…”

“…This seems to be the case for Cn12. It is not toxic in vivo at concentrations at which other toxins from the same scorpion, such as Cn2 (a mammalian-specific toxin), Cn5 (a crustacean-specific toxin) and Cn10 (an insectspecific toxin) are very effective (doses of 0.4-40 lg per individual [57,58]). As shown in Fig.…”