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.


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.


CONCLUSIONS
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.
Ohkura
Kazuto
K
Department of Biological Science and Technology, Faculty of Engineering, University of Tokushima, Japan. kohkura@sag.bekkoame.ne.jp
Nagamune
Hideaki
H
Kourai
Hiroki
H
D000595:Amino Acid Sequence; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000737:chemistry; D001430:Bacteriocins; D018360:Crystallography, X-Ray; D003603:Cytotoxins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D004910:Erythrocyte Membrane / Q000737:chemistry / Q000378:metabolism; D006460:Hemolysin Proteins; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D001430:Bacteriocins; D003603:Cytotoxins; D006460:Hemolysin Proteins; C403910:intermedilysin protein, Streptococcus intermedius; C020452:Clostridium perfringens theta-toxin