title: Perfringolysin O structure and mechanism of pore formation as a paradigm for cholesterol-dependent cytolysins.
abstract: Cholesterol-dependent cytolysins (CDCs) constitute a family of pore forming toxins secreted by Gram-positive bacteria. These toxins form transmembrane pores by inserting a large β-barrel into cholesterol-containing membrane bilayers. Binding of water-soluble CDCs to the membrane triggers the formation of oligomers containing 35-50 monomers. The coordinated insertion of more than seventy β-hairpins into the membrane requires multiple structural conformational changes. Perfringolysin O (PFO), secreted by Clostridium perfringens, has become the prototype for the CDCs. In this chapter, we will describe current knowledge on the mechanism of PFO cytolysis, with special focus on cholesterol recognition, oligomerization, and the conformational changes involved in pore formation.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Massachusetts, 710 N. Pleasant St., Lederle GRT, Amherst, MA, 01003, USA.
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Johnson
authors.forename: Alejandro P
authors.initials: AP
authors.lastname: Heuck
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001427:Bacterial Toxins / Q000737:chemistry*; D002462:Cell Membrane / Q000737:chemistry*; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism; D003603:Cytotoxins / Q000737:chemistry / Q000502:physiology; D006460:Hemolysin Proteins / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D001427:Bacterial Toxins; D003603:Cytotoxins; D006460:Hemolysin Proteins; C020452:Clostridium perfringens theta-toxin; D002784:Cholesterol