Complement C8B

The complement system enhances the immune defense by producing the cell-killing membrane attack complex (MAC), a pore protein composed of C5b, C6, C7, C8, and C9. Complement component 8 (C8), the most complex constitutive of the MAC, is a heterotrimer protein consisting of genetically distinct proteins, C8A (α chain), C8B (β chain), and C8G (γ chain). Human C8B is a 591-amino acid 67 kDa polypeptide, which is independently encoded by the C8B gene. C8B is homologous to C8A, which also contains a ~40 kDa MAC perforin (MACPF) domain, two thrombospondin modules, an LDL-related module, and an epidermal growth factor module. It has been researched that the MACPF domain of C8B involves at least two binding reactions, one is noncovalently bound to C8A with high affinity, the other is responsible for integrating C8 protein with the pre-assembled C5b-7 complex to form MAC.

In humans, C8B mutation is a rare autosomal recessive disorder causing complement component 8 deficiency type II and complement component 6 deficiency. Patients with C8B deficiency suffer from severe recurrent infections, particularly Neisseria gonorrhoeae or Neisseria meningitidis infections.

Fig. 1 Structure of complement component C8 complex.¹

Reference

1. From Wikipedia: By SchauderCM - Own work, CC BY-SA 3.0 https://commons.wikimedia.org/wiki/File:3OJY.png