The Helix Ring Peptide U 11 from the Venom of the Ant, Tetramorium bicarinatum , Acts as a Putative Pore-Forming Toxin.

An insect neuroactive helix ring peptide called U 11 -MYRTX-Tb1a (abbreviated as U 11 ) from the venom of the ant, Tetramorium bicarinatum . U 11 is a 34-amino-acid peptide that is claimed to be one of the most paralytic peptides ever reported from ant venoms acting against blowflies and honeybees. The peptide features a compact triangular ring helix structure stabilized by a single disulfide bond, which is a unique three-dimensional scaffold among animal venoms. Pharmacological assays using Drosophila S2 cells have demonstrated that U 11 is not cytotoxic but instead suggest that it may modulate potassium channels via the presence of a functional dyad. In our work described here, we have tested this hypothesis by investigating the action of synthetically made U 11 on a wide array of voltage-gated K and Na channels since it is well known that these channels play a crucial role in the phenomenon of paralysis. Using the Xenopus laevis oocyte heterologous expression system and voltage clamp, our results have not shown any modulatory effect of 1 μM U 11 on the activity of Kv1.1, Kv1.3, Kv1.4, Kv1.5, Shaker IR, Kv4.2, Kv7.1, Kv10.1, Kv11.1 and KQT1, nor on DmNav and BgNav. Instead, 10 μM U 11 caused a quick and irreversible cytolytic effect, identical to the cytotoxic effect caused by Apis mellifera venom, which indicates that U 11 can act as a pore-forming peptide. Interestingly, the paralytic dose (PD 50 ) on blowflies and honeybees corresponds with the concentration at which U 11 displays clear pore-forming activity. In conclusion, our results indicate that the insecticidal and paralytic effects caused by U 11 may be explained by the putative pore formation of the peptide.