Attack Mechanism

The attack mechanism of complement (1) has been defined as those complement proteins the binding of which to the target membrane is necessary for the production of membrane damage. I t is distinguished from the recognition and activation mechanisms of complement which, although capable of attaching to the target cell, may act from the fluid phase or from the surface of another cell. Earlier work (2) demonstrated that the attack mechanism is comprised of five different components, namely C5,1 C6, C7, C8, and C9. The present study was designed to obtain information which pertains to the molecular arrangement of these five proteins on a membrane under attack by complement. The accumulated evidence strongly suggests that the membrane-bound attack mechanism consists of a compact decamolecular assemblage with a total molecular weight of approximately 1 million. Previous investigations have shown a requirement of protein binding to the target cell for expression of hemolytic activity for C5 (3-5), C6 (6, 7), 2 C8(8), and C9 (9). They have also pointed out a functional interdependence between C5, C6, and C7 (3), particularly in the formation of ECS, 6, 73 (2, 6). In addition, these three proteins were found to have an affinity for each other in free solution, enabling them to enter into reversible protein-protein interactions (3).2 Such interaction has recently been demonstrated to occur also between C8 and C9. 4 Thus information published to date raised