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

2003/09/19 by Kara S. Giddings, Arthur E. Johnson, Rodney K. Tweten · 7 citations
Medicine · Biochemistry, Genetics and Molecular Biology · #Streptococcal Infections and Treatments #Erythrocyte Function and Pathophysiology #Lipid Membrane Structure and Behavior

paper · doi:10.1073/pnas.2033520100

openalex publication_date 2003/09/19 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01

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 beta-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.

Citations

• 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 Spectroscopy
• Monomer-Monomer Interactions Drive the Prepore to Pore Conversion of a β-Barrel-forming Cholesterol-dependent Cytolysin
• Site-directed mutagenesis by overlap extension using the polymerase chain reaction
• The Mechanism of Membrane Insertion for a Cholesterol-Dependent Cytolysin
• Arresting Pore Formation of a Cholesterol-dependent Cytolysin by Disulfide Trapping Synchronizes the Insertion of the Transmembrane β-Sheet from a Prepore Intermediate
• Systematic risk behavior of financially distressed firms

Cited by

• Characterization of a Streptococcal Cholesterol-Dependent Cytolysin with a Lewis y and b Specific Lectin Domain
• Cholesterol Exposure at the Membrane Surface Is Necessary and Sufficient to Trigger Perfringolysin O Binding
• The Cholesterol-Dependent Cytolysin Signature Motif: A Critical Element in the Allosteric Pathway that Couples Membrane Binding to Pore Assembly
• Bacterial pore-forming toxins: The (w)hole story?
• The Cholesterol-Dependent Cytolysin Family of Gram-Positive Bacterial Toxins
• Monomer-Monomer Interactions Propagate Structural Transitions Necessary for Pore Formation by the Cholesterol-dependent Cytolysins
• Cholesterol-dependent cytolysin [wikipedia]