2012/05/30 by Eileen M. Hotze, Elizabeth M. Wilson-Kubalek, Allison J. Farrand +4 · 1 citation
Biochemistry, Genetics and Molecular Biology · Chemistry · Medicine · #Barrel (horology) #Biochemistry #Biology #Biophysics #Chemistry #Crystallography #Cytolysin #Lipid Membrane Structure and Behavior #Lipid bilayer #Materials science #Membrane #Monomer #Oligomer #Organic chemistry #Polymer #Polymer chemistry #RNA and protein synthesis mechanisms #Streptococcal Infections and Treatments
paper · pdf · doi:10.1074/jbc.m112.380139
openalex publication_date 2012/05/30 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/04
The assembly of the cholesterol-dependent cytolysin (CDC) oligomeric pore complex requires a complex choreography of secondary and tertiary structural changes in domain 3 (D3) of the CDC monomer structure. A point mutation was identified in the archetype CDC, perfringolysin O, that blocks detectable D3 structural changes and traps the membrane-bound monomers in an early and reversible stage of oligomer assembly. Using this and other mutants we show that specific D3 structural changes are propagated from one membrane-bound monomer to another. Propagation of these structural changes results in the exposure of a β-strand in D3 that allows it to pair and form edge-on interactions with a second β-strand of a free membrane-bound monomer. Pairing of these strands establishes the final geometry of the pore complex and is necessary to drive the formation of the β-barrel pore. These studies provide new insights into how structural information is propagated between membrane-bound monomers of a self-assembling system and the interactions that establish the geometry of the final pore complex. Background: The cholesterol-dependent cytolysins (CDCs) undergo a complex set of structural transitions to form the homo-oligomeric pore complex. Results: Structural transitions are propagated between monomers of the oligomeric complex. Conclusion: Specific structural changes establish the geometry of the oligomeric pore complex and promote the completion of existing oligomers. Significance: CDCs use membrane binding and ordered intermolecular interactions to drive assembly of their β-barrel pore.