Multiple Parameters Beyond Lipid Binding Affinity Drive Cytotoxicity of Cholesterol-Dependent Cytolysins

The cholesterol-dependent cytolysins.

In view of the recent studies on the CDCs, a reasonable schematic of the stages leading to membrane insertion of the CDCs can be assembled. As shown in Fig. 3, we propose that the CDC first binds to the membrane as a monomer. These monomers then diffuse laterally on the membrane surface to encounter other monomers or incomplete oligomeric complexes. Presumably, once the requisite oligomer size ...

What planar lipid membranes tell us about the pore-forming activity of cholesterol-dependent cytolysins.

Pore-forming toxins are an important group of natural molecules that damage cellular membranes by forming transmembrane pores. They are used by many organisms for attack or defense and similar proteins are employed in the immune system of vertebrates. Various biophysical approaches have been used to understand how these proteins act at the molecular level. One of the most useful, in terms of mo...

Cholesterol-dependent cytolysins, a family of versatile pore-forming toxins.

A New Model for Pore Formation by Cholesterol-Dependent Cytolysins

Cholesterol Dependent Cytolysins (CDCs) are important bacterial virulence factors that form large (200-300 Å) membrane embedded pores in target cells. Currently, insights from X-ray crystallography, biophysical and single particle cryo-Electron Microscopy (cryo-EM) experiments suggest that soluble monomers first interact with the membrane surface via a C-terminal Immunoglobulin-like domain (Ig;...

How cholesterol-dependent cytolysins bite holes into membranes.

In a show piece for electron microscopy (EM), Tilley at al. used single-particle cryo-EM to visualize the structural rearrangements in the bacterial toxin pneumolysin that occur when it assembles into a membrane-associated prepore and when the prepore subsequently transitions into a fully membrane-inserted pore.