Ectatomma tuberculatum has one of the most toxic venoms known among ants. A total of 48 proteins have been identified within the venom of these ants. A neurotoxin,, is responsible for the major toxic effect of the venom in mammals and insects.
Structure
Ectatomin is a highly basic toxin and contains with an internal disulfide bridge in each chain that forms a hairpin. In aqueous solution ectatomin forms a four-alpha helix bundle.
Channel Formation
Ectatomin has channel-forming activity. It forms nonselective cation channels in membrane systems and the channel formation depends on membrane potentials and occurs only at a positive cis-potential. Each pore is formed by two ectatomin molecules. This channel-forming property of ectatomin may account partially for its toxic activity. The high level of ectatomin’s toxicity implies that there may be specific cellular targets for its action.
Many pore forming toxins have similar mechanisms. The toxin recognizes the cell membrane by either a specific receptor or by the direct interactions with the membrane lipids. After the toxin binds with the cell membrane, the protein undergoes a considerable conformational change to form the pore.
Ectatomin is inserted effectively and efficiently into the plasma membrane at a concentration of 5 x 10-7 M and does not penetrate through the cell membranes.
Hemolytic and Cytolytic Effects
Hemolytic activities of ectatomin were determined in rabbit erythrocytes with 78 HU*mg-1 and 41 HU*mg-1 . The cytolytic activity of ectatomin was observed in Sf9 cells and was (2 +/- 0.8) x 10-6 M. These hemolytic and cytolytic effects are seen at high concentrations (0.5 x 10-6 to 10-5). At these high concentrations, ectatomin damages cell membranes in a detergent-like or pore-forming fashion. This supports that the binding of the ectatomin to cell membranes is nondescriminative; it involves lipids rather than specific receptor molecules.
Effect on Cardiac Ca2+ Channels
Ectatomin has inhibitory effects on cardiac Ca2+ channels. These inhibitory effects occur at concentrations of 10-11 to 10-8 M. The inhibitions at specific concentrations suggest that there is a specific receptor, which could possibly be the Ca2+ channels. Ectatomin modulates the activity of calcium channels and blocks calcium channels. Although it is not only limited to the blockage of the calcium channels. It is also possible that ectatomin interacts directly or allosterically with β-adrenergic receptors in their agonist-occupied state. The mechanism is not clear, but this interaction may limit the receptor to transition to its agonist-free state.
Inhibiting Autophosphorylation
Ectatomin has inhibitory effects on autophosphorylation in calcium channels. There are at least two distinct phosphorylation sites that are known for the channels. The inhibition of both phosphorylation sites has the same effect on the calcium channels. The inhibition causes the channels to stay open and the become nonspecific. Ions may flow freely.
Additional Resources
Proposed mechanism for pore formation
References
Nolde, D. E., et al. “Three-Dimensional Structure of Ectatomin from Ectatomma Tuberculatum Ant Venom.” Journal Of Biomolecular NMR, vol. 5, no. 1, Jan. 1995, pp. 1–13. EBSCOhost, search.ebscohost.com/login.aspx?direct=true&db=mdc&AN=7881269&site=eds-live&scope=site.
Pluzhnikov, K., et al. “Analysis of Ectatomin Action on Cell Membranes.” European Journal Of Biochemistry, vol. 262, no. 2, June 1999, pp. 501–506. EBSCOhost, search.ebscohost.com/login.aspx?direct=true&db=mdc&AN=10336635&site=eds-live&scope=site.
Pluzhinikov KA, Nol'de DE, Tertyshnikova SM, et al. [Structure-activity study of the basic toxic component of venom from the ant Ectatomma tuberculatum] Bioorganicheskaia Khimiia. 1994 Aug-Sep;20(8-9):857-871.
Silva, Juliana Rocha da, et al. “Assessing the Proteomic Activity of the Venom of the Ant Ectatomma Tuberculatum (Hymenoptera: Formicidae: Ectatomminae).” Psyche: A Journal of Entomology, June 2018, pp. 1–11. EBSCOhost, doi:10.1155/2018/7915464.
