C3c Human
Description
Structure and Composition of C3c
C3c is a proteolytic fragment of C3, the most abundant complement protein in human plasma (1.2 mg/mL) . Its structure includes:
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Beta chain: A single chain linked to the alpha chain via disulfide bonds.
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Alpha chain fragments: Post-cleavage fragments (alpha’1 and alpha’2) retained via disulfide bonds .
C3c has a total molecular weight of 137 kDa and retains the beta chain intact while containing two alpha-chain fragments .
Activation and Cleavage Pathways
C3c is generated during complement activation via two pathways:
Classical Pathway
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C4b2a convertase cleaves C3 into C3a (anaphylatoxin) and C3b.
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Factor I (with cofactor H) cleaves C3b into C3c (beta chain + alpha’1 + alpha’2) and C3d (alpha’3 fragment) .
Alternative Pathway
| Pathway | Convertase | Cleavage Products | Function |
|---|---|---|---|
| Classical | C4b2a | C3a, C3b → C3c, C3d | Antibody-mediated immune complex clearance |
| Alternative | C3bBb | C3a, C3b → C3c, C3d | Direct pathogen recognition and clearance |
C3c lacks the C3d domain required for receptor binding (e.g., CR2), limiting its role in opsonization .
Clinical Significance as a Biomarker
C3c levels are measured to assess complement activation and predict disease outcomes.
Heart Failure
A study of 197 patients with stable systolic heart failure found:
| Parameter | Normal C3c (n=163) | Elevated C3c (n=33) | P-value |
|---|---|---|---|
| All-cause mortality | 22 (14%) | 1 (3%) | 0.001 |
| LVEF | Lower | Slightly higher | – |
| NT-proBNP | Higher | Lower | – |
Elevated C3c correlated with improved survival and reduced adverse remodeling, suggesting a protective role in cardiac repair .
Inflammatory and Autoimmune Diseases
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SLE: Low C3 levels (due to consumption) indicate disease activity .
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Glomerulonephritis: C3c elevation signals complement-mediated kidney damage .
Measurement and Analytical Methods
C3c is quantified using immuno-nephelometry, leveraging monoclonal antibodies specific to its beta chain .
Bio-Rad’s monoclonal antibody (clone 013E-498.2.3) targets the ~135 kDa C3c beta chain, ensuring specificity . Siemens Healthineers’ N Antiserum to Human C3c uses rabbit-derived antibodies for nephelometric assays .
Functional Roles in Immune Regulation
C3c modulates immune responses through:
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Immune Tolerance: C3d (a C3c fragment) enhances antigen presentation by binding CR2 receptors on B cells, promoting antibody diversification .
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Inflammation: C3a (a byproduct of C3 cleavage) recruits neutrophils and induces mast cell degranulation .
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Pathogen Evasion: Overexpression of C3c may suppress complement activation, aiding microbial survival .
Research and Therapeutic Implications
Product Specs
Product Science Overview
The complement system consists of over 30 proteins that circulate in the blood and tissue fluids. These proteins are primarily produced by the liver and are involved in a cascade of reactions that enhance the ability of antibodies and phagocytic cells to clear pathogens from an organism. The system can be activated through three pathways: the classical pathway, the lectin pathway, and the alternative pathway .
Complement Component 3 is central to the activation of the complement system. It is the most abundant complement protein in the blood and is essential for the activation of all three pathways. Upon activation, C3 is cleaved into two fragments: C3a and C3b. C3a acts as an anaphylatoxin, which means it can induce inflammation by stimulating mast cells and basophils to release histamine. C3b, on the other hand, binds to the surface of pathogens, marking them for destruction by phagocytes .
Complement Component C3c is formed when C3b is further cleaved by factor I, a regulatory protein. This cleavage results in the formation of C3c and C3dg. C3c is a significant fragment because it retains the ability to bind to receptors on phagocytic cells, thus facilitating the clearance of immune complexes and apoptotic cells .
The primary function of C3c is to aid in the opsonization and clearance of pathogens and immune complexes. It plays a vital role in the immune response by enhancing phagocytosis. Additionally, the levels of C3c in the blood can be used as a biomarker for various diseases. For instance, decreased levels of C3c are often observed in patients with autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. Conversely, elevated levels may indicate acute inflammation or infection .
The measurement of C3c levels in the blood is commonly used in clinical diagnostics to assess the activity of the complement system. It is particularly useful in diagnosing and monitoring autoimmune diseases. Research on C3c also provides insights into the mechanisms of immune regulation and the development of therapeutic interventions for immune-related disorders .
