Complement C8A

Complement component 8 (C8) plays an essential role in the assembly of membrane attack complex (MAC), the effector of the complement system that can lyse the target cells. As a functional complement protein, C8 is a heterotrimer protein composed of three subunits, α chain, β chain, and γ chain, in which complement C8A (C8A) is the α chain of C8. Human C8A is a 584-amino acid 65 kDa polypeptide, composed of a MAC perforin domain and other four modules (two thrombospondin modules, an LDL-related module, and an epidermal growth factor module). The MAC perforin domain of C8A has a characterized L-shaped fold that is similar to bacterial cholesterol-dependent cytolysins, which contains two regions (transmembrane b hairpin 1 (TMH1) and TMH2) responsible for insert into the target membrane. And the N-terminal of C8A lies a binding site for the γ chain that covalently links to C8G through a disulfide bond.

Mutations in the C8A gene cause complement C8 deficiency type I, a rare autosomal recessive inheritance disease, leading to increased susceptibility to recurrent bacterial infections, especially neisserial infections. C8A deficiency also closely associates with immunodeficiency due to a late component of complement deficiency.

Fig. 1 C8A is a part of MAC pore structure.¹

Reference

1. Menny, Anaïs, et al. "CryoEM reveals how the complement membrane attack complex ruptures lipid bilayers." Nature communications 9.1 (2018): 5316.