Complement component 3
C3 is the most abundant complement component. It is a component of the alternative complement pathway, and is synthesised mainly in the liver. Cleavage of C3 into C3a and C3b is central to complement activation and can occur by the:
The cleaved C3b molecule exposes several binding sites, including a thioester one which is relocated to a position adjacent to the first macroglobulin domain. C3b attaches to target surfaces such as pathogens and binds to factor B. Factor B is then cleaved. This produces a C3bBb complex which has C3 convertase activity. More C3 is then cleaved, amplifying the response and leading to C3b2 complexes with C5 convertase activity.
- The C3 S/F (Arg80Gly) polymorphism of its gene have a strong association with age-related macular degeneration and outcome in renal transplantation. In this last case C3 S/S allotype in the donor kidney transplanted into C3S homozygotes predicted poorer transplant survival. Individuals can have the C3 S/S allotype (CC genotype), C3 S/F allotype (CG genotype, about 10% in white populations) and C3 F/F allotype (GG genotype).
- C3F is associated with:
- C3 deficient mice do not have choriodal neovasculation after appropriate stimulation to produce this in normal mice.
- ↑ Yates JR, Sepp T, Matharu BK, Khan JC, Thurlby DA, Shahid H, Clayton DG, Hayward C, Morgan J, Wright AF, Armbrecht AM, Dhillon B, Deary IJ, Redmond E, Bird AC, Moore AT. Complement C3 variant and the risk of age-related macular degeneration. The New England journal of medicine. 2007 Aug 9; 357(6):553-61.(Link to article – subscription may be required.)
- ↑ Brown KM, Kondeatis E, Vaughan RW, Kon SP, Farmer CK, Taylor JD, He X, Johnston A, Horsfield C, Janssen BJ, Gros P, Zhou W, Sacks SH, Sheerin NS. Influence of donor C3 allotype on late renal-transplantation outcome. The New England journal of medicine. 2006 May 11; 354(19):2014-23.(Link to article – subscription may be required.)