Monomer-monomer interactions drive the prepore to pore conversion of a beta-barrel-forming cholesterol-dependent cytolysin.
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.
Hotze
Eileen M
EM
Department of Microbiology and Immunology, the University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
Heuck
Alejandro P
AP
Czajkowsky
Daniel M
DM
Shao
Zhifeng
Z
Johnson
Arthur E
AE
Tweten
Rodney K
RK
D001427:Bacterial Toxins / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D004735:Energy Transfer; D005978:Glutathione / Q000378:metabolism; D006460:Hemolysin Proteins; D013050:Spectrometry, Fluorescence; D001614:beta-Amylase / Q000378:metabolism
D001427:Bacterial Toxins; D006460:Hemolysin Proteins; C020452:Clostridium perfringens theta-toxin; D002784:Cholesterol; D001614:beta-Amylase; D005978:Glutathione