Complement component 3


Complement component 3, often simply called C3, is a protein of the immune system. It plays a central role in the complement system and contributes to innate immunity. In humans it is encoded on chromosome 19 by a gene called C3.

Function

C3 plays a central role in the activation of the complement system. Its activation is required for both classical and alternative complement activation pathways. People with C3 deficiency are susceptible to bacterial infection.
One form of C3-convertase, also known as C4b2a, is formed by a heterodimer of activated forms of C4 and C2. It catalyzes the proteolytic cleavage of C3 into C3a and C3b, generated during activation through the classical pathway as well as the lectin pathway. C3a is an anaphylotoxin and the precursor of some cytokines such as ASP, and C3b serves as an opsonizing agent. Factor I can cleave C3b into C3c and C3d, the latter of which plays a role in enhancing B cell responses. In the alternative complement pathway, C3 is cleaved by C3bBb, another form of C3-convertase composed of activated forms of C3 and factor B. Once C3 is activated to C3b, it exposes a reactive thioester that allows the peptide to covalently attach to any surface that can provide a nucleophile such as a primary amine or a hydroxyl group. Activated C3 can then interact with factor B. Factor B is then activated by factor D, to form Bb. The resultant complex, C3bBb, is called the alternative pathway C3 convertase.
C3bBb is deactivated in steps. First, the proteolytic component of the convertase, Bb, is removed by complement regulatory proteins having decay-accelerating factor activity. Next, C3b is broken down progressively to first iC3b, then C3c + C3dg, and then finally C3d. Factor I is the protease that performs these cuts but it requires the help of another protein to supply cofactor activity.

Structure

Several crystallographic structures of C3 have been determined and reveal that this protein contains 13 domains.

Biochemistry

Biosynthesis

In humans, C3 is predominantly synthesised by liver hepatocytes and to some degree by epidermis keratinocytes.

Clinical use

Levels of C3 in the blood may be measured to support or refute a particular medical diagnosis. For example, low C3 levels are associated with Systemic Lupus Erythematosus
and some types of kidney disease such as post-infectious glomerulonephritis, membranoproliferative glomerulonephritis, and shunt nephritis.

Interactions

Complement component 3 has been shown to interact with Factor H.

Pathology

Deficiencies in C3 lead to genetic infections, usually fatal to the newborn.