Complement C9

Complement C9 is a glycosylated protein with a 71KDa molecular weight and made up of a single polypeptide chain. C9 functions by binding to the C5b-8 complex and generate the mature membrane attack complex (MAC) on cell membranes. The MAC contains seven components: C5b, C6, C7, C8 (C8a, C8b, and C8g), and C9.

Three pathways of complement activation produce proteolytic enzyme complexes (C3/C5 convertases) and them enzymes cleave a peptide bond in the larger alpha chain of C5 leading to the release of the anaphylatoxin C5a and activating C5b. This is the only proteolytic step in the generation of the C5b-9 complex. Besides, not all C5b-8 complexes have complete rings of C9, usually, the C5b-9 complex has three C9 on average. However, these structures can result in lysis if enough are produced in a given cell. Completed protein rings of C9 generate the pores seen on electron micrographs and leading to the leakage of metabolites and small proteins out of the cell as well as the movement of water into the cell. This process may finally cause cell death. In addition, a previous study showed that C9 subunits of the MAC penetrate the hydrocarbon core of the lipid bilayer more deeply than any other subunit of the MAC.

Fig 1. The structure of the MAC.¹

Reference

1. From Wikipedia: By SLiva2016 - Own work, CC BY-SA 3.0 https://commons.wikimedia.org/wiki/File:Membrane_Attack_Complex_(Terminal_Complement_Complex_C5b-9).png