Complement C5b

C5b is the first complement component to initiate MAC formation. As the three pathways of complement produce proteolytic enzyme complexes (C3/C5 convertases) which are bound to the target surface, these enzymes cleave a peptide bond in the larger alpha chain of C5 leading to the release of C5a and activating C5b. The C5b fragment is intrinsically labile and if not binds to C6, it will become inactive within 2 minutes. Furthermore, C5b,6 complex remains bound to the C3/C5 convertase until it binds a single C7 molecule. And in the absence of the C7 protein, C5b,6 is released into the fluid phase. The C5b67 complex is rendered lipophilic and is drawn into the phospholipid bilayer of the cell membrane or viral envelope. During complement activation, some C5b,6 diffuses away from the target cell and may, after combining with C7, enter the membrane of a nearby cell.

C5b–C7 binds to the plasma membrane via a hydrophobic site on C7 becoming exposed so that it can be inserted into the lipid bilayer of the cell membrane. After that, C8 binds to the C5b-C7 complex and C9 binds to C8 within the C5b-C8 complex, resulting in C9 undergoing a conformational change that causes the exposure of a hydrophobic domain that made C9 insertion by the membrane lipid bilayer.

Fig.1 Three extracellular complement initiation pathways culminate in a common terminal pathway. (Girardi, 2020)

Reference

1. Girardi, G., et al. Essential role of complement in pregnancy: from implantation to parturition and beyond. Frontiers in immunology. 2020, 11, 1681.