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Complement factor I

Definition:

Trypsin-like serine protease that plays an essential role in regulating the immune response by controlling all complement pathways. Inhibits these pathways by cleaving three peptide bonds in the alpha-chain of C3b and two bonds in the alpha-chain of C4b thereby inactivating these proteins. Essential cofactors for these reactions include factor H and C4BP in the fluid phase and membrane cofactor protein/CD46 and CR1 on cell surfaces. The presence of these cofactors on healthy cells allows degradation of deposited C3b by CFI in order to prevent undesired complement activation, while in apoptotic cells or microbes, the absence of such cofactors leads to C3b-mediated complement activation and subsequent opsonization.

References:

[1]. R A Harrison, et al. The physiological breakdown of the third component of human complement. Mol Immunol. 1980 Jan;17(1):9-20. [Content Brief]

[2]. Maria L Barilla-LaBarca, et al. Role of membrane cofactor protein (CD46) in regulation of C4b and C3b deposited on cells. J Immunol. 2002 Jun 15;168(12):6298-304. [Content Brief]

[3]. Krisztina K Timár, et al. Human keratinocytes produce the complement inhibitor factor I: Synthesis is regulated by interferon-gamma. Mol Immunol. 2007 Apr;44(11):2943-9. [Content Brief]

[4]. Xiaoguang Xue, et al. Regulator-dependent mechanisms of C3b processing by factor I allow differentiation of immune responses. Nat Struct Mol Biol. 2017 Aug;24(8):643-651. [Content Brief]

[5]. T Seya, et al. Regulation of proteolytic activity of complement factor I by pH: C3b/C4b receptor (CR1) and membrane cofactor protein (MCP) have different pH optima for factor I-mediated cleavage of C3b. J Biochem. 1990 Feb;107(2):310-5. [Content Brief]

[6]. A Sahu, et al. Interaction of vaccinia virus complement control protein with human complement proteins: factor I-mediated degradation of C3b to iC3b1 inactivates the alternative complement pathway. J Immunol. 1998 Jun 1;160(11):5596-604. [Content Brief]

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