The cholesterol-dependent cytolysins.

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

Redefining cholesterol's role in the mechanism of the cholesterol-dependent cytolysins.

The cholesterol-dependent cytolysins (CDCs) constitute a large family of pore-forming toxins that function exclusively on cholesterol-containing membranes. A detailed analysis of the various stages in the cytolytic mechanism of three members of the CDC family revealed that significant depletion of cholesterol from the erythrocyte membrane stalls these toxins in the prepore complex. Therefore, t...

Structural Basis for Receptor Recognition by the Human CD59-Responsive Cholesterol-Dependent Cytolysins.

Cholesterol-dependent cytolysins (CDCs) are a family of pore-forming toxins that punch holes in the outer membrane of eukaryotic cells. Cholesterol serves as the receptor, but a subclass of CDCs first binds to human CD59. Here we describe the crystal structures of vaginolysin and intermedilysin complexed to CD59. These studies, together with small-angle X-ray scattering, reveal that CD59 binds ...

Perfringolysin O structure and mechanism of pore formation as a paradigm for cholesterol-dependent cytolysins.

Cholesterol-dependent cytolysins (CDCs) constitute a family of pore forming toxins secreted by Gram-positive bacteria. These toxins form transmembrane pores by inserting a large β-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 β-hairp...

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...

Insights into the action of the superfamily of cholesterol-dependent cytolysins from studies of intermedilysin.

The cholesterol-dependent cytolysins (CDCs), a superfamily of pore-forming toxins, are characterized by a conserved undecapeptide motif that is believed to be critical for membrane recognition by means of cholesterol. Intermedilysin (ILY), an unusual member of the CDCs, exhibits specificity for human cells and contains nonconservative substitutions in the motif. We show that the cellular specif...