Structural Analysis of Human Specific Cytolysin Intermedilysin Aiming Application to Cancer Immunotherapy

Background: Intermedilysin (ILY) is a human specific cytolysin secreted by Streptococcus intermedius. In the present study, we performed molecular modeling of ILY and cholesterol-dependent cytolysins (CDCs) (pneumolysin, PLY; listeriolysin O, LLO; streptolysin O, SLO; alveolysin, ALV; suilysin, SLY; pyolysin, PLO) to compare the membrane binding domains including the undecapeptide (11mer) region which is thought to be necessary for the cytolytic activity of CDCs. Materials and Methods: The molecular models of cytolysins were constructed using InsightII with Homology module with X-ray data of perfringolysin O (PFO). Results: The ILY molecule was long and rod shaped, and comprised four domains. ILY was shown to possess stereocomplementary surfaces within the molecule and the potential to stack with 8 degrees of curvature leading to a ring cluster of 45 molecules or so in the human erythrocyte cell membranes. Conclusion: From the molecular orbital calculations and isostatic potential analysis, we considered that the ILY 11mer region has different features from those of traditional CDCs, and the ILY domain 4 should be very useful to apply the human cell-specific targeting module.