title: Mechanism of complement cytolysis and the concept of channel-forming proteins.
abstract: Complement damages membranes via the terminal reaction sequence that leads to the formation of membrane-bound, macromolecular C5b-9(m) protein complexes. These complexes represent C5b-8 monomers to which varying numbers of C9 molecules can be bound. Complexes carrying high numbers of C9 (ca. 6/8-12/16?) exhibit the morphology of hollow protein channels. Because they are embedded within the lipid bilayer, aqueous transmembrane pores are generated that represent the primary lesions caused by complement in the target cell membrane. Many other proteins damage membranes by forming channels in a manner analogous to the C5b-9(m) complex. Two prototypes of bacterial exotoxins, Staphylococcus aureus alpha-toxin and streptolysin-O, are discussed in this context, and attention is drawn to the numerous analogies existing among these protein systems. Common to all is the process of self-association of the native proteins to form supramolecular complexes. This event is in turn accompanied by a unique transition of the molecules from a hydrophilic to an amphiphilic state.
mesh_terms: D000818:Animals; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000032:analysis; D002462:Cell Membrane / Q000648:ultrastructure; D002470:Cell Survival; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000502:physiology*; D006460:Hemolysin Proteins; D005779:Immunodiffusion; D007123:Immunoelectrophoresis, Two-Dimensional; D007473:Ion Channels / Q000502:physiology*; D008854:Microscopy, Electron; D008954:Models, Biological; D008970:Molecular Weight; D013301:Streptolysins / Q000032:analysis
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D015938:Complement Membrane Attack Complex; D006460:Hemolysin Proteins; D007473:Ion Channels; D013301:Streptolysins; C021091:staphylococcal alpha-toxin; C025964:streptolysin O; D003165:Complement System Proteins