Figure 1.

Overview of C5 complement activation. Complement C5 activation can occur either by the classical, lectin and alternate complement pathways to generate C5 convertases, or via proteases extrinsic to the complement pathway. C5 convertases or extrinsic proteases can cleave C5 to form proteolytic fragments C5a and C5b. C5a is a potent anaphylatoxin that is rapidly deactivated by removal of the C terminal arginine to form C5adesArg. C5a binds with high affinity (thick black arrows) to both C5aR1 and C5aR2 receptors, while C5adesArg binds with high affinity to the C5aR2 receptor and with low affinity (dashed arrow) to the C5aR1 receptor. The C5aR1 receptor primarily drives pro–inflammatory effects, while the C5aR2 receptor can mediate pro– or anti–inflammatory effects depending on its cellular context. In the absence of cell associated complement inhibitors, C5b interacts with a single copy of complement proteins C6, C7, C8 and a further 18 copies of C9 to form a pore within the cell membrane called the membrane attack complex (MAC).⁸ The MAC can lyse certain Gram–negative bacteria, promoting bacterial clearance, while host cells can avoid lysis due to the presence of membrane associated complement regulators.