MODULATION OF alpha-TOXIN BINDING BY MEMBRANE COMPOSITION

Although the alpha-toxin from S. aureus was the first pore-forming toxin identified, its mode of interaction with membranes is still not fully understood. The toxin forms heptameric pores on cellular and artificial membranes. The present hypothesis is that the initial binding to the membrane occurs with low affinity, and that an efficient oligomerisation, relying on clusters of binding sites, is the reason for the overall high affinity of the binding process. In order to separate the effects of increasing concentration of binding sites from this topological effect, we investigated the oligomer formation based on pyrene-fluorescence for a series of lipid compositions, where the fraction of toxin binding lipids (egg phospatidylcholine (ePC) or egg sphingomyelin (eSM)) was varied while their concentration remained constant. The results indicate that an increased local density of toxin binding sites occurring due to phase separation facilitates oligomer formation. Furthermore, the change in local environment (number of neighboring cholesterol molecules) upon domain formation also enhances oligomer formation.

We thank the DFG (SFB 490) for financial support, S.Bhakdi and A.Valeva for production of the toxin and helpful discussions.