Perfringolysin O Structure and Mechanism of Pore Formation as a Paradigm for Cholesterol-Dependent Cytolysins

摘要

Cholesterol-dependent cytolysins (CDCs) constitute a family of pore forming toxins secreted by Gram-positive bacteria. These toxins form trans-membrane pores by inserting a large beta-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 beta-hairpins into the membrane requires multiple structural conformational changes. Perfringolysin O (PFO), secreted by Clostridium per-fringens, 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.