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 [PMID:6019133]. 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 [PMID: 6912277]. 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 [PMID:9642242,2387864]. 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) [PMID:21454577]. 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.