Equinatoxin II (EqtII) is a 179-residue toxin from the venom of the sea anemone Actinia equina. EqtII is a member of the actinoporin family of proteins, which have potent lytic activity towards membranes containing sphingomyelin (SM). To gain insight into the atomic-level details governing SM selectivity, a series of all-atom molecular dynamics simulations were performed to model the binding of EqtII to micelles of n-dodecylphosphocholine (DPC) and DPC/SM. These models are in good agreement with concurrent high-resolution solution NMR studies and prior data [1, 2] that suggests membrane binding is dependent on a conserved cluster of aromatic amino acids. From this groundwork study, further simulations will be performed to investigate EqtII oligomerisation and membrane insertion to determine the mechanism of pore formation.
1. Anderluh G, Razpotnik A, Podlesek Z, Maček P, Separovic F, Norton RS. (2005) Interaction of the eukaryotic pore-forming cytolysin equinatoxin II with model membranes: 19F NMR studies. J. Mol. Biol. 347:27-39.
2. Bakrač B, Gutiérrez-Aguirre I, Podlesek Z, Sonnen AFP, Gilbert RJC, Maček P, Lakey JH, Anderluh G. (2008) Molecular determinants of sphingomyelin specificity of a eukaryotic pore-forming toxin. J. Biol. Chem. 283:18665-77.