Mechanism of membrane damage by streptolysin-O.
Streptolysin-O (SLO) is a thiol-activated, membrane-damaging protein toxin of Mr 69,000 that is produced by most strains of beta-hemolytic group A streptococci. Native, primarily water-soluble toxin molecules bind to cholesterol-containing target membranes to assemble into supramolecular curved rod structures (25 to 100 nm long by ca. 7.5 nm wide), forming rings and arcs that penetrate into the apolar domain of the bilayer. Electron microscopic analyses of toxin polymers in their native and reconstituted membrane-bound form indicate that the convex surface of the rod structures is a hydrophobic, lipid-binding domain, whereas the concave surfaces appear to be hydrophilic. The embedment of the rings and arcs generates large transmembrane slits or pores of up to 30-nm diameter that can be directly visualized by negative staining and freeze-fracture electron microscopy. SLO oligomers were isolated in extensively delipidated form in detergent solution, and cholesterol was found not to detectably contribute to the observed rod structures. The rods are stable structures that resist prolonged exposure to trypsin and chymotrypsin. They can be reincorporated into cholesterol-free phosphatidylcholine liposomes to generate lesions identical to those observed on erythrocytes lysed by native SLO. Thus, although cholesterol plays a key role in the initial binding of SLO to the membrane, it does not directly participate in the formation of the membrane-penetrating toxin channels. Membrane damage by SLO is basically analogous to that mediated by previously studied channel formers, namely, the C5b-9 complement complex and staphylococcal alpha-toxin.
D000818:Animals; D001426:Bacterial Proteins; D004591:Electrophoresis, Polyacrylamide Gel; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000648:ultrastructure; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008081:Liposomes; D008854:Microscopy, Electron; D008970:Molecular Weight; D010713:Phosphatidylcholines; D011817:Rabbits; D012756:Sheep; D013297:Streptococcus pyogenes; D013301:Streptolysins / Q000302:isolation & purification / Q000633:toxicity*
D001426:Bacterial Proteins; D008081:Liposomes; D010713:Phosphatidylcholines; D013301:Streptolysins; C025964:streptolysin O