Complement C3 | Elisa - Clia - Antibody - Protein

Background

Complement component 3 (C3) is a central protein in the complement system, a crucial part of the immune system that enhances the ability to clear pathogens and damaged cells, promotes inflammation, and attacks the pathogen's cell membrane. C3 is the most abundant complement protein in the plasma and plays a pivotal role in the activation of the complement system. Its importance is underscored by its involvement in all three pathways of complement activation: the classical pathway, the lectin pathway, and the alternative pathway.

Protein Structure

• Domain Composition: C3 is a large glycoprotein composed of 1,663 amino acids with a molecular weight of approximately 185 kDa. It is initially synthesized as a single polypeptide and later cleaved into two chains, C3α and C3β, which are held together by disulfide bonds.
• Key Functional Domains:
• Anaphylatoxin (C3a): The C3a fragment is released during activation and functions as an anaphylatoxin, inducing inflammation.
• C3b: The larger fragment, C3b, covalently binds to pathogen surfaces, marking them for destruction and facilitating opsonization.

Classification and Subtypes

• Primary Forms: C3 is primarily present in two forms: native C3 (before activation) and activated fragments (C3a and C3b).
• Functional Derivatives: Upon activation, C3b can further undergo proteolytic cleavage to form iC3b, C3c, and C3dg, each with distinct roles in immune regulation.

Function and Biological Significance

• Opsonization: C3b binds to microbial surfaces, tagging pathogens for phagocytosis by immune cells.
• Formation of C5 Convertase: C3b participates in the formation of C5 convertase, a crucial enzyme complex in the complement cascade that leads to the generation of the membrane attack complex (MAC).
• Immune Clearance: C3b helps in the clearance of immune complexes and apoptotic cells by binding to complement receptors on phagocytes.
• Inflammation: C3a acts as a potent inflammatory mediator by binding to C3a receptors on various immune cells, inducing chemotaxis, degranulation, and other inflammatory responses.

Clinical Issues

• Complement Deficiencies: Deficiencies in C3 can lead to increased susceptibility to recurrent bacterial infections, particularly with encapsulated bacteria.
• Autoimmune Diseases: Abnormal activation of C3 is implicated in autoimmune diseases such as systemic lupus erythematosus (SLE), where immune complexes are not effectively cleared.
• Age-related Macular Degeneration (AMD): Genetic variants in the C3 gene have been associated with an increased risk of AMD, a leading cause of blindness in the elderly.
• Therapeutic Target: C3 is a target for therapeutic intervention in diseases characterized by complement-mediated damage, such as paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS).

Summary

Complement C3 is an essential protein in the immune system, acting at the heart of the complement cascade to mediate various immune responses. Its activation leads to the generation of fragments that facilitate pathogen opsonization, inflammation, and cell lysis. Clinical implications of C3 involve susceptibility to infections, autoimmune diseases, and certain age-related conditions, highlighting its significance in both health and disease. Therapeutic modulation of C3 activity holds potential for treating complement-mediated disorders.