Structures of perfringolysin O suggest a pathway for activation of cholesterol-dependent cytolysins.

ABSTRACT: Cholesterol-dependent cytolysins (CDCs), a large family of bacterial toxins, are secreted as water-soluble monomers and yet are capable of generating oligomeric pores in membranes. Previous work has demonstrated that large scale structural rearrangements occur during this transition but the detailed mechanism by which these changes take place remains a puzzle. Despite evidence of structural and functional couplings between domains 3 and 4, the crystal structure of the CDC, perfringolysin O (PFO), shows the two domains do not make direct contact. Here, we present crystal structures of PFO that demonstrate movements of domain 4 are sufficient to trigger conformational changes that are transmitted through the molecule to the distant domain 3. These coupled movements result in a loss of many c

SUBMITTER: Rossjohn J 

PROVIDER: S-EPMC3674820 | biostudies-literature | 2007 Apr

REPOSITORIES: biostudies-literature