MOLECULAR MODELING OF AMOEBAPORE AND NK-LYSIN - A 4-ALPHA-HELIX BUNDLE MOTIF OF CYTOLYTIC PEPTIDES FROM DISTANTLY RELATED ORGANISMS

Background: Amoebapore of the protozoan Entamoeba histolytica and NK-l ysin of porcine cytotoxic lymphocytes are effector peptides from organ isms separated extremely early in their evolutionary paths. The peptid es intrigued us, however, with indications of some functional similari ty. We thus wanted to derive and compare predictions for their as yet unknown three-dimensional structures as a guide for and to be tested b y further experiments. Results: Molecular models were generated by use of a genetic algorithm that selects according to basic protein struct ure principles exploiting available information such as the primary st ructures, secondary structure predictions and positions of disulfide b onds. Topological differences aside, the structural motif of an antipa rallel four-alpha-helix bundle with adjacent connections and intramole cular crosslinks is predicted for both types of peptides. It combines the feature of amphipathic alpha-helices with a disulfide-bonded compa ct structure known from the beta-sheeted defensins and small toxins. C onclusions: The models presented here strengthen the notion that amoeb apore and NK-lysin are particular among cytolytic and antibacterial po lypeptides and share a similar function and structural motif. They als o allow experimental testing and a better comparison of the two protei ns in view of the predicted similarities and differences of their resp ective folds.