title: Insights into the action of the superfamily of cholesterol-dependent cytolysins from studies of intermedilysin.
abstract: The cholesterol-dependent cytolysins (CDCs), a superfamily of pore-forming toxins, are characterized by a conserved undecapeptide motif that is believed to be critical for membrane recognition by means of cholesterol. Intermedilysin (ILY), an unusual member of the CDCs, exhibits specificity for human cells and contains nonconservative substitutions in the motif. We show that the cellular specificity of ILY is based on its ability to specifically bind to human cells and does not involve some other feature of the CDC mechanism. Furthermore, cellular recognition by ILY appears to be encoded in domain 4 alone but does not involve the variant undecapeptide of ILY. We show that the undecapeptide is involved in the prepore-to-pore conversion of ILY and so demonstrate a direct connection between the structure of the undecapeptide and the prepore-to-pore transition. We have determined the crystal structure of ILY, which, when compared to the known structure of a prototypical CDC, suggests that the basic aspects of its 3D structure are likely to be conserved in all CDCs.
authors.affiliation: Biota Structural Biology Laboratory, St. Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065, Australia.
authors.forename: Galina
authors.initials: G
authors.lastname: Polekhina
authors.forename: Kara Sue
authors.initials: KS
authors.lastname: Giddings
authors.forename: Rodney K
authors.initials: RK
authors.lastname: Tweten
authors.forename: Michael W
authors.initials: MW
authors.lastname: Parker
mesh_terms: D020816:Amino Acid Motifs; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001430:Bacteriocins; D001665:Binding Sites; D002463:Cell Membrane Permeability / Q000187:drug effects; D002477:Cells; D002784:Cholesterol / Q000378:metabolism*; D018360:Crystallography, X-Ray; D003603:Cytotoxins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D040681:Structural Homology, Protein
chemical_list: D001426:Bacterial Proteins; D001430:Bacteriocins; D003603:Cytotoxins; C403910:intermedilysin protein, Streptococcus intermedius; D002784:Cholesterol