Sandbox Reserved 996

Ectatomin (1eci) is the main component of venom of the ant Ectatomma tuberculatum, making up 15%-18% of the crude venom and accounting for 90% of the venom's toxicity.^[1] When bitten by E. tuberculatum, Ectatomin inserts into the target's cell membranes and forms a nonselective cation channel.^[2] The calculated isoelectric point and molecular weight are 9.95 and 7928 Da, respectively.^[1]

Structure

Biologically, Ectatomin exists as a heterodimer stabilized by linkages. The has 37 amino acid residues, while the has 34 amino acid residues. The structure of Ectatomin was solved using 2D NMR and CHARMm computational optimization, though there are 20 similar proposed models in total.^[3]

Generally, each subunit is composed of two α-helices, linked by disulfide bonds, with a connecting hairpin hinge region. The two subunits are linked by a disfulide bond between their hairpin hinge regions. One α-helix from each subunit is kinked approximately 40°, due to the presence of . The kinked α-helix of the α subunit is more kinked, containing three proline residues, while the kinked α-helix of the β subunit only contains one proline residue.^[3]

The internal region between the two subunits is primarily composed of hydrophobic residues.

Sequence - α subunit - GVIPKKIWETVCPTVEPWAKKCSGDIATYIKRECGKL^[2]

Sequence - β subunit - WSTIVKLTICPTLKSMAKKCEGSIATMIKKKCDK^[2]

Mechanism

Ectatomin has several proposed mechanisms of action. The primary proposed mechanism involves the formation of a nonselective cation channel. In this mechanism, the α and β subunits open up, exposing the internal hydrophobic residues. The protein flattens while remaining attached at the hairpin hinge region. The now exposed hydrophobic residues nonselectively insert into plasma membranes. The inserted protein dimerizes, eventually forming a nonselective cation channel.

For the second and third proposed mechanisms of action, Ectatomin has also been shown to inhibit kinases, specifically protein tyrosine kinase and protein kinase C, and Ca2+ channels. Kinase inhibition would potentially allow Ectatomin to interfere with various components of signal transduction. Calcium channel inhibition would potentially allow Ectatomin to affect physiological processes such as contraction, neurotransmitter release and neuronal activity regulation.

Toxicology

^[3]

^[3]

^[4]