Complement component 9 (C9) is the last protein that binds to the assembling membrane attack complex (MAC) of complement, completing the sequence of events that leads to the destruction of target membranes. Although lysis of erythrocytes occurs even without C9, its presence increases the rate of hemolysis.
C9-mediated hemolysis is a relatively slow and temperature sensitive reaction and has therefore been attributed to an enzymatic action of complement C9. Multiple C9 molecules bind to C5b-8 in forming the membrane attack complex (MAC), and it has been postulated that the C9 to C8 ratio determines the size of transmembrane channels formed by C5b-9. Studies with photoactivatable membrane-restricted probes suggested that C9 subunits of the membrane attack complex (MAC) penetrate the hydrocarbon core of the lipid bilayer more deeply than does any other subunit of the membrane attack complex (MAC). Complement C9 within the membrane-bound MAC is also accessible from the aqueous phase, suggesting that the MAC-associated C9 extends from the hydrophilic phase into the hydrocarbon phase of the membrane.
Ultrastructural studies demonstrated that formation of the ring-like membrane lesion caused by complement is entirely dependent on C9 and that C9 mediates the fusion of two C5b-8 complexes to the characteristic ring structure of the dimeric membrane attack complex (MAC). Both C5b-9 dimerization and C9-mediated hemolysis are temperature-sensitive reactions, suggesting an important role of C9 for dimer formation in the cytolytic reaction. The dimeric nature of the MAC was supported by molecular weight studies and by molecular hybridization experiments. Some studies indicated a tendency of the MAC to form MAC oligomers. In contrast, other groups suggested a monomeric C5b-9 composition of the membrane attack complex (MAC).
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