Conformational Changes That Effect Oligomerization and Initiate Pore Formation Are Triggered throughout Perfringolysin O upon Binding to Cholesterol

摘要: Pore formation by the cholesterol-dependent cytolysins (CDCs) requires presence of cholesterol in target membrane. Cholesterol was long thought to be cellular receptor for these toxins, but not all CDCs require binding. Intermedilysin, secreted Streptococcus intermedius, only binds membranes containing human protein CD59 forms pores if membrane contains sufficient cholesterol. In contrast, perfringolysin O (PFO), Clostridium perfringens, substantial amounts Given that different steps assembly various CDC cholesterol, here we have analyzed what extent molecules, themselves, can modulate conformational changes associated with PFO oligomerization and pore formation. when dispersed aqueous solution, this binding triggers distant rearrangement a β-strand exposes an interface. Moreover, upon prepore complex, unfolds two amphipathic transmembrane β-hairpins, positions their nonpolar surfaces so they associate hydrophobic surface. The interaction is therefore initiate irreversible sequence coupled extend throughout toxin molecule.