title: Inactivation and activity of cholesterol-dependent cytolysins: what structural studies tell us.
abstract: The homologous bacterially expressed cholesterol-dependent cytolysins (CDCs) form pores via oligomerization; this must occur preferentially once the target membrane has been engaged. Conformational changes in CDCs then drive partition from an aqueous environment to a lipidic one. This review addresses how premature oligomerization is prevented, how conformational changes are triggered, and how cooperativity between subunits brings about new functionality absent from isolated protomers. Variations are found in the answers provided by the CDCs to these issues. Some toxins use pH as a trigger of activity, but recent results have shown that dimerization in solution is an alternative way of preventing premature oligomerization, in particular for the CDC from Clostridium perfringens, perfringolysin. More controversially, there is still no resolution to the debate as to whether incomplete (arciform) oligomers form pores: recent results again suggest that they do.
authors.affiliation: Division of Structural Biology, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford, OX3 7BN, United Kingdom. gilbert@strubi.ox.ac.uk
authors.forename: Robert J C
authors.initials: RJ
authors.lastname: Gilbert
mesh_terms: D002784:Cholesterol / Q000502:physiology*; D003016:Clostridium perfringens / Q000472:pathogenicity / Q000502:physiology*; D003603:Cytotoxins / Q000737:chemistry / Q000502:physiology*; D019281:Dimerization; D017434:Protein Structure, Tertiary
chemical_list: D003603:Cytotoxins; D002784:Cholesterol