Molecular Profiles of Cholesterol-dependent Cytolysin Family-derived 11mer Regions

Background: Cholesterol-dependent cytolysins (CDCs) are secreted from various types of bacteria and are involved in various diseases (e.g. abscess formation). Traditional CDCs has a conserved 11mer region, which is a key structure in membrane recognition. Materials and Methods: Based on the X-ray data of traditional CDC perfringolysin O (PFO), molecular models of intermedilysin (ILY), pyolysin (PLO), vaginolysin (VLY), and Streptococcus mitis-derived human platelet aggregation factor (Sm-hPAF) were constructed. The 11mer regions of these models were extracted, and their molecular features were analyzed. Results: The dipole moments of these 11mer regions were classified into four types, and their stereo-hydrophobicity (dGW) was different. It was thought that these results influenced the species specificity and membrane recognition of each cytolysin. Conclusion: Traditional CDCs, ILY, PLO, and VLY consisted of four domains (domains 1 to 4). Domain 0 existed on the N-terminal side in Sm-hPAF in addition to these four domains. The 11mer sequence of Sm-hPAF is the same as that of VLY, but Sm-hPAF has slightly different characteristics (e.g. species specificity, membrane recognition, cholesterol dependency) compared to VLY. Dynamic structure analysis of domain 0 might clarify these differences. Some bacteria-derived cytolytic toxins, such as perfringolysin O (PFO), pneumolysin (PLY), streptolysin O (SLO), listeriolysin O (LLO), alveolysin (ALV), and suilysin (SLY) form clusters on target cell membranes and lyse cells by pore formation (1, 2). Their cytolytic activity is cholesterol-dependent, and they are called cholesterol- dependent cytolysins (CDCs). CDCs have been found in various bacterial strains (e.g. Clostridium perfringens: PFO, Streptococcus pneumoniae: PLY, Streptococcus pyogenes: SLO: Listeria monocytogenes: LLO, Bacillus alvei: ALV, Streptococcus suis: SLY). CDC family members have a conserved undecapeptide (11mer) region, the amino acid sequence of which is ECTGLAWEWWR. These traditional CDC 11mer regions play a key role in cell membrane recognition (3-5). Intermedilysin (ILY) was found to be secreted from