Molecular Biology Commons^™

Cholesterol Exposure At The Membrane Surface Is Necessary And Sufficient To Trigger Perfringolysin O Binding, John J. Flanagan, Rodney K. Tweten, Arthur E. Johnson, Alejandro P. Heuck

Alejandro P. Heuck

Perfringolysin O (PFO) is the prototype for the cholesterol-dependent cytolysins, a family of bacterial pore-forming toxins that act on eukaryotic membranes. The pore-forming mechanism of PFO exhibits an absolute requirement for membrane cholesterol, but the complex interplay between the structural arrangement of the PFO C-terminal domain and the distribution of cholesterol in the target membrane is poorly understood. Herein we show that PFO binding to the bilayer and the initiation of the sequence of events that culminate in the formation of a transmembrane pore depend on the availability of free cholesterol at the membrane surface, while changes in the acyl …