Complement C8G

Complement component 8 (C8), a heterotrimer protein composed of three different subunits, α chain, β chain, and γ chain, is one of the five complement components of the cytolytic membrane attack complex (MAC). The γ chain, also known as C8G, is a 202-amino acid 22 kDa polypeptide encoded by the C8G gene. Different from C8A and C8B, human C8G is a single domain polypeptide independent of any complement protein, which is a member of the lipocalin family capable of binding small hydrophobic ligands. Although the Cys 40 of C8G is attached to the Cys 164 of C8A through a disulfide bond, C8G is not essential for both the structure and function of MAC. As a lipocalin, C8G contains a typical lipocalin fold with a distinct binding site for small molecules, such as retinol, steroids, and fatty acids.

Different from the human C8A and C8B genes that are closely linked on chromosome 1p, the human C8G gene is located on chromosome 9q. Mutations in the C8G gene associates with immunodeficiency due to a late component of complement deficiency. Besides, C8G deficiency also has been reported to play important role in Acute Salpingo-Oophoritis, a reproductive disease related to salpingo-oophoritis and pyelonephritis.

Fig. 1 C8G 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.