Complement factor H (CFH) is an essential regulator for normal complement activity, which negatively inhibits the alternative pathway and complement amplification. CFH is a large plasma protein encoded by the CFH gene. Human CFH is a 155 kDa heavily glycoprotein composed of 20 complement control protein (CCP) domains (or short consensus repeats), each of which consists of around 60 amino acids with 2 disulfides (CysI-CysIII and CysII-CysIV). The adjacent domains are connected by three to eight residues. The N-terminal CCP1-4 are responsible for the binding to C3b and also act as a cofactor for complement factor I to catalyze C3b proteolysis. The CCP7 and C-terminal CCP19-20 contain binding sites for C3b, C3d, sialic acid, and glycosaminoglycans, which are responsible for anchoring CFH to the host surface.
When binds to glycosaminoglycans and or sialic acids on host cells, CFH acts as a soluble inhibitor to prevent complement activation on host cell surfaces.
CFH functions as a cofactor for complement factor I to regulate proteolytic degradation of already-deposited C3b.
CFH accelerate the decay of C3 convertase C3bBb in the complement alternative pathway, thereby decreasing or inhibiting the formation of C3b.
CFH also mediates multiple cellular responses through binding to specific receptors, such as complement receptor 3.
The abnormal expression or mutations of CFH directly cause complement dysfunctions, leading to various disorders, including autoimmune diseases, age-related macular degeneration, atypical hemolytic uremic syndrome, schizophrenia, and increased susceptibility to infections.
Fig. 1 The structure of CFH.1
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Reference
From Wikipedia: Deposition authors: Jaakola, V.-P., Jokiranta, T.S., Goldman, A.; visualization author: User:Astrojan, CC BY-SA 4.0 https://commons.wikimedia.org/wiki/File:2g7i.jpg
Fig. 1 The structure of CFH.1