Redefining cholesterol's role in the mechanism of the cholesterol-dependent cytolysins
Open Access
- 19 September 2003
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 100 (20) , 11315-11320
- https://doi.org/10.1073/pnas.2033520100
Abstract
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, the depletion of membrane cholesterol prevents the insertion of the transmembrane β-barrel and pore formation. These unprecedented findings provide a paradigm for the involvement of cholesterol in the CDC cytolytic mechanism and that of other pore-forming toxins whose activity is enhanced by the presence of membrane cholesterol.Keywords
This publication has 42 references indexed in Scilit:
- The Mechanism of Membrane Insertion for a Cholesterol-Dependent CytolysinCell, 1999
- Cross-Linking of Plasmalemmal Cholesterol in Lymphocytes Induces Capping, Membrane Shedding, and Endocytosis through Coated PitsBiochemical and Biophysical Research Communications, 1999
- Identification of a Membrane-Spanning Domain of the Thiol-Activated Pore-Forming Toxin Clostridium perfringens Perfringolysin O: An α-Helical to β-Sheet Transition Identified by Fluorescence SpectroscopyBiochemistry, 1998
- Alteration of the Myometrial Plasma Membrane Cholesterol Content with .beta.-Cyclodextrin Modulates the Binding Affinity of the Oxytocin ReceptorBiochemistry, 1995
- Interaction of .theta.-Toxin (Perfringolysin O), a Cholesterol-Binding Cytolysin, with Liposomal Membranes: Change in the Aromatic Side Chains upon Binding and InsertionBiochemistry, 1995
- Role of the stereochemistry of the hydroxyl group of cholesterol and the formation of nonbilayer structures in phosphatidylethanolaminesBiochemistry, 1989
- Staphylococcal α‐toxin increases the permeability of lipid vesicles by cholesterol‐ and pH‐dependent assembly of oligomeric channelsEuropean Journal of Biochemistry, 1989
- Site-directed mutagenesis by overlap extension using the polymerase chain reactionGene, 1989
- Protease‐nicked O‐toxin of Clostridium perfringens, a new memnrane probe with no cytoltic effect, revcals two classes of cholesterol as toxin‐binding sites on sheep erythrocytesEuropean Journal of Biochemistry, 1988
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976