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
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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.
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