Mechanism of membrane insertion of a multimeric beta-barrel protein: perfringolysin O creates a pore using ordered and coupled conformational changes.
Perfringolysin O, a bacterial cytolytic toxin, forms unusually large pores in cholesterol-containing membranes by the spontaneous insertion of two of its four domains into the bilayer. By monitoring the kinetics of domain-specific conformational changes and pore formation using fluorescence spectroscopy, the temporal sequence of domain-membrane interactions has been established. One membrane-exposed domain does not penetrate deeply into the bilayer and is not part of the actual pore, but is responsible for membrane recognition. This domain must bind to the membrane before insertion of the other domain into the bilayer is initiated. The two domains are conformationally coupled, even though they are spatially separated. Thus, cytolytic pore formation is accomplished by a novel mechanism of ordered conformational changes and interdomain communication.
Heuck
A P
AP
Department of Medical Biochemistry and Genetics Texas A&M University, College Station, TX 77843, USA.
Hotze
E M
EM
Tweten
R K
RK
Johnson
A E
AE
D001427:Bacterial Toxins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism / Q000494:pharmacology; D003016:Clostridium perfringens; D006460:Hemolysin Proteins; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D010743:Phospholipids / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D013997:Time Factors
D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D008051:Lipid Bilayers; D008081:Liposomes; D010743:Phospholipids; C020452:Clostridium perfringens theta-toxin; D002784:Cholesterol