Monomer-Monomer Interactions Drive the Prepore to Pore Conversion of a β-Barrel-forming Cholesterol-dependent Cytolysin

2002/03/01 by Eileen M. Hotze, Alejandro P. Heuck, Daniel M. Czajkowsky +3 · 9 citations
Medicine · Biochemistry, Genetics and Molecular Biology · #Streptococcal Infections and Treatments #Antibiotic Resistance in Bacteria #Antimicrobial Resistance in Staphylococcus

paper · pdf · doi:10.1074/jbc.m111039200

openalex publication_date 2002/03/01 · openalex created_date 2016/06/24 · openalex updated_date 2026/08/01

Abstract

Perfringolysin O (PFO), a cholesterol-dependent cytolysin, forms large oligomeric pore complexes comprised of up to 50 PFO molecules. In the present studies a mutant of PFO (PFO(Y181A)) has been identified that traps PFO in a multimeric prepore complex that cannot insert its transmembrane beta-hairpins and therefore cannot form a pore. Remarkably, PFO(Y181A) can be induced to insert its transmembrane beta-hairpins if functional PFO is incorporated into the PFO(Y181A) oligomeric prepore complex. Furthermore, the transition from prepore to pore appears to be an "all or none" process; partial insertion of the transmembrane beta-barrel does not occur. Therefore, cooperative interactions between the monomers of the prepore drive the prepore to pore conversion that results in the formation of the transmembrane beta-barrel.

Citations

• Structure of a Cholesterol-Binding, Thiol-Activated Cytolysin and a Model of Its Membrane Form
• Versatility of the mitochondrial protein import machinery
• 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

Cited by

• Vertical collapse of a cytolysin prepore moves its transmembrane β‐hairpins to the membrane
• Prepore to pore transition of a cholesterol-dependent cytolysin visualized by electron microscopy
• The Cholesterol-Dependent Cytolysin Signature Motif: A Critical Element in the Allosteric Pathway that Couples Membrane Binding to Pore Assembly
• Redefining cholesterol's role in the mechanism of the cholesterol-dependent cytolysins
• Monomer-Monomer Interactions Propagate Structural Transitions Necessary for Pore Formation by the Cholesterol-dependent Cytolysins
• Structural insights into the membrane-anchoring mechanism of a cholesterol-dependent cytolysin
• Membrane-dependent conformational changes initiate cholesterol-dependent cytolysin oligomerization and intersubunit β-strand alignment
• The Cholesterol-Dependent Cytolysin Family of Gram-Positive Bacterial Toxins
• Cholesterol-dependent cytolysin [wikipedia]