Complement C5 | Elisa - Clia - Antibody - Protein

Background

Complement component 5 (C5) is a critical protein in the complement system, part of the innate immune system that enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells from the organism, promote inflammation, and attack the pathogen's cell membrane. The C5 protein is synthesized as a single polypeptide that is cleaved into two chains, C5a and C5b, upon activation. The C5 gene is located on chromosome 9 and encodes a precursor protein of approximately 190 kDa.

The complement system is divided into three pathways: the classical, lectin, and alternative pathways. All three pathways converge at the activation of C3, which subsequently leads to the activation of C5. This activation is a pivotal event in the complement cascade, resulting in the generation of C5a, an anaphylatoxin, and C5b, which initiates the formation of the membrane attack complex (MAC).

Protein Structure

• Molecular Weight: C5 is a glycoprotein with a molecular weight of approximately 190 kDa.
• Subunits: The protein consists of two polypeptide chains, alpha (α) and beta (β), which are linked by a disulfide bond.
• Activation Site: C5 is cleaved by C5 convertase into C5a and C5b.
• C5a: A small, potent anaphylatoxin involved in inflammatory responses.
• C5b: Initiates the assembly of the terminal complement complex (TCC), also known as the MAC, which creates pores in the membranes of target cells.

Classification and Subtypes

• Isoforms: No major isoforms; however, genetic variants and polymorphisms can affect C5 function and expression.
• Pathways: C5 is central to all three complement activation pathways (classical, lectin, and alternative).

Function and Biological Significance

• C5a: Acts as a powerful chemotactic factor, attracting immune cells to sites of infection and promoting inflammation. It can also induce degranulation of mast cells and basophils, leading to the release of histamine and other mediators.
• C5b: Binds to C6 and C7 to form a complex that attaches to target cell membranes, subsequently binding C8 and multiple C9 molecules to form the MAC. The MAC forms transmembrane channels, leading to cell lysis and death.

Clinical Issues

• Deficiency: C5 deficiency can lead to increased susceptibility to recurrent bacterial infections, particularly with Neisseria species.
• Dysregulation: Overactivation of C5 can contribute to various inflammatory and autoimmune diseases, such as paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS).
• Therapeutic Targeting: C5 inhibitors, such as eculizumab, have been developed to treat diseases involving excessive complement activation. These inhibitors block the cleavage of C5, thereby preventing the formation of C5a and C5b.

Summary

Complement component 5 (C5) plays a crucial role in the immune system by participating in the formation of the membrane attack complex and mediating inflammatory responses through the generation of C5a. The protein's activity is essential for host defense mechanisms against infections, but dysregulation can lead to pathological conditions. Understanding the structure, function, and clinical implications of C5 has led to significant advancements in treating complement-mediated diseases.