Complement system (Homo sapiens)

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The complement activation takes place through one or more of the well-established (alternative, classical or lectin) pathways consisting of plasma and membrane-bound proteins. All three pathways converge at the level of complement C3 [ref.2] and are controlled by regulators [ref.17].

Complement C3 belongs to the α2-macroglobulin family of proteins, and consists of a β-chain and an α-chain. Cleavage of C3 which can be initiated by one or more of the above three distinct pathways, into C3b[Proteolysis@23-667,749-1663] and C3a [Proteolysis@672-748] is an important step in the complement activation cascade. Classical and lectin pathways, when activated with recognition of pathogens (or immune complexes) use C3-convertase [C4b2a] to cleave complement C3 into C3a and C3b. However, in alternative pathway a small fraction of the C3 molecules are hydrolyzed to C3(H20) exposing new binding sites. This hydrated C3 [C3(H20)] recruits complement factor B [fB], which is then cleaved by complement factor D [fD] to result in formation of the minor form of C3-convertase [C3(H20)Bb] that cleaves C3 into C3a and C3b. Further, addition of C3b to C3 convertase [C3bBb or C4b2a] results in C5 convertase [C3bBb3b or C4b2a3b], that cleaves complement C5 to C5a and C5b, is the last enzymatic step of the complement activation cascade. During complement activation C5b interacts with complement C6, C7, C8 and C9 in a sequential and non-catalyzed manner to result in the formation of Terminal Complement Complex (TCC). The entire network is considered as a simple recognition and elimination system of host-immune complexes and apoptotic and/or pathogens, and therefore promotes host immune homeostasis. The complement system is also involved in cross-talk with other processes related to coagulation, lipid metabolism and cancer. However, many pathogens counteract complement attack through a range of different mechanisms, such acquisition of host complement regulators to the surface of pathogen, or secretion of complement inactivation factors. In order to have a holistic view of the entire complement network, Dr. John D.Lambris group (University of Pennsylvania) developed the Complement Map Database (CMAP) which is a unique repository focused on documented molecular interactions described within the complement cascade and between complement and other biological systems. Information contained in CMAP (http://www.complement.us/cmap/index.php) is entirely based on published experimental data and is fully revised by experts in the field. Further, the Signaling Gateway Molecule Pages (SGMP, www.signalinggateway.org, ref.3) has published a curated data on each protein involved in human complement activation pathways (refs 2, 4-16).

1. Yang K, Dinasarapu AR, Reis ES, Deangelis RA, Ricklin D, Subramaniam S, Lambris JD. CMAP: Complement Map Database. Bioinformatics 2013 Jul 15;29(14):1832-1833.
2. Dinasarapu AR, Chandrasekhar A, Sahu A, Subramaniam S (2012) Complement C3. UCSD Molecule Pages, 1 (2), 34-48. (doi: 10.6072/H0.MP.A004235.01).
3. Dinasarapu AR, Saunders B, Ozerlat I, Azam K and Subramaniam S. (2011) Signaling Gateway Molecule Pages - a data model perspective. Bioinformatics, 27(12), 1736-1738.
4. Chandrasekhar A, Dinasarapu AR, Tenner AJ and Subramaniam S (2012) Complement C1q subcomponent subunit A. UCSD Molecule Pages, 1 (2), 49-60. (doi: 10.6072/H0.MP.A004228.01).
5. Dinasarapu AR, Chandrasekhar A, Fujita T, Subramaniam S (2013) Mannose/mannan-binding lectin. UCSD Molecule Pages, 2 (1), 8-18. (doi: 10.6072/H0.MP.A004276.01).
6. Dinasarapu AR, Chandrasekhar A, J‚àö‚â•zsi M, Subramaniam S (2012) Complement factor H. UCSD Molecule Pages, 1 (2), 71-86. (doi: 10.6072/H0.MP.A004256.01).
7. Chandrasekhar A, Dinasarapu AR, Isenman D.E, Subramaniam S (2012) Complement C5. UCSD Molecule Pages , 1 (2), 61-70.(doi: 10.6072/H0.MP.A004240.01).
8. Chandrasekhar A, Dinasarapu AR, Matsushita M, Subramaniam S (2013) MAp44. UCSD Molecule Pages.(doi: 10.6072/H0.MP.A008392.01).
9. Chandrasekhar A, Dinasarapu AR, Matsushita M, Subramaniam S (2013) MASP-3. UCSD Molecule Pages.(doi: 10.6072/H0.MP.A008391.01).
10. Chandrasekhar A, Dinasarapu AR, Matsushita M, Subramaniam S (2013) MASP-1. UCSD Molecule Pages.(doi: 10.6072/H0.MP.A004274.01).
11. Chandrasekhar A, Dinasarapu AR, Thielens N, Subramaniam S (2013) MASP-2. UCSD Molecule Pages.(doi: 10.6072/H0.MP.A004275.01).
12. Chandrasekhar A, Dinasarapu AR, Thiel S, Subramaniam S (2013) L-Ficolin. UCSD Molecule Pages, 2 (1), 37-44.(doi: 10.6072/H0.MP.A004266.01).
13. Chandrasekhar A, Dinasarapu AR, Cedzyaski M, Subramaniam S (2013) H-Ficolin. UCSD Molecule Pages.(doi: 10.6072/H0.MP.A004267.01).
14. Dinasarapu AR, Chandrasekhar A, Hajishengallis G, Subramaniam S (2013) Integrin beta-2. UCSD Molecule Pages.(doi: 10.6072/H0.MP.A004263.01).
15. Dinasarapu AR, Chandrasekhar A, Inal J, Subramaniam S (2013) Complement C2. UCSD Molecule Pages.(doi: 10.6072/H0.MP.A004234.01).
16. Min J, Chandrasekhar A, Dinasarapu AR, Kemper C, Subramaniam S (2014) Properdin. UCSD Molecule Pages.(doi: 10.6072/H0.MP.A004258.01).

17. Ricklin D, Hajishengallis G, Yang K, Lambris JD. (2010). Complement: a key system for immune surveillance and homeostasis. Nature Immunology 11: 785- 97.