Dinasarapu , A.R. and Chandrasekhar , A. and Sahu , A. and Subramaniam, S. (2012) Complement C3 Basis Sequence: Human. In: UCSD Molecule Pages. UCSD SIGNALING-GATEWAY , pp. 1-10.

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Abstract

The central component of the complement system is C3 molecule, consisting of a β-chain and an α-chain connected by cysteine bridges. Cleavage of C3 into C3b and C3a is a pivotal step in the complement activation cascade, which can be initiated by three distinct pathways — the classical (CP), the lectin (LP) and the alternative (AP) pathway. The AP is antibody independent and relies on native C3 undergoing minimal spontaneous hydrolysis of thioester bond, represented by C3(H20). Complement factor B (fB), when bound to C3(H20), is cleaved by complement factor D (fD) into Ba and Bb. C3(H20)Bb, a fluid phase C3-convertase, is responsible for a constant low level of C3 cleavage into C3a and C3b (tick-over) (Nilsson et al. 2012). C3b can bind covalently, via its reactive thioester, to cell surface carbohydrates or immune aggregates (opsonization). When C3b binds to an appropriate surface then fB associates with C3b and is cleaved by fD to form C3bBb, which is a highly efficient C3-convertase. Classical and lectin complement pathways use complement components C4 and C2 for C3-convertase of form C4b2a (Müller-Eberhard et al. 1967). Upon binding to pathogen or apoptotic cell surface, C3-convertases (C3bBb and C4b2a) can induce amplification of the alternative pathway. Thus, the AP might account for up to 80-90% of total complement activation, even when initially triggered by the classical or lectin pathway (Harboe and Mollnes 2008). The prolonged activation of complement pathways results in addition of one more molecule of C3b to C3 convertases to form C5 convertases: C3(H20)Bb3b, C3bBb3b and C4b2a3b (Rawal and Pangburn 2001; Rawal and Pangburn 2003). C3-convertases selectively cleave C3 at Arg-/-Ser bond in C3α-chain to form C3a and the α-chain portion of C3b (Nagasawa et al. 1985). Further, C3b undergoes successive proteolytic cleavages leading to inactive C3 products. These steps are mediated by complement factor I (fI) and lead to generation of iC3b, C3d/C3dg, C3c and C3f. Functions of C3 and each of its cleavage products are listed below:

Item Type:	Book Section
Subjects:	Infection and Immunity
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	09 Apr 2015 09:48
Last Modified:	16 May 2015 07:55
URI:	http://nccs.sciencecentral.in/id/eprint/28

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