Complement component 5

Formation of the Membrane Attack Complex (MAC) involving Complement Component 5

Complement Component 5 (C5) is a crucial protein in the complement system, which is part of the immune system that enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promotes inflammation, and attacks the pathogen's cell membrane. C5 plays a pivotal role in the formation of the membrane attack complex (MAC), which is essential for the lysis of pathogens.

Structure

C5 is a large glycoprotein composed of two chains, the alpha and beta chains, linked by a disulfide bond. The protein is synthesized in the liver and circulates in the blood as an inactive precursor. Upon activation, C5 is cleaved into two fragments: C5a and C5b.

Function

The primary function of C5 is to initiate the formation of the MAC. The cleavage of C5 into C5a and C5b is a critical step in the complement cascade.

• C5a: This is a potent anaphylatoxin that acts as a powerful chemotactic factor, attracting neutrophils and other immune cells to the site of infection. It also increases vascular permeability and induces smooth muscle contraction.
• C5b: This fragment initiates the assembly of the MAC by binding sequentially to C6, C7, C8, and multiple C9 molecules, forming a pore in the target cell membrane, leading to cell lysis.

Role in Disease

Dysregulation of C5 can lead to various diseases. Overactivation of C5 can contribute to autoimmune diseases and chronic inflammatory conditions, while deficiencies in C5 can result in increased susceptibility to infections, particularly by Neisseria species.

Therapeutic Target

C5 is a target for therapeutic intervention in diseases characterized by excessive complement activation. Eculizumab, a monoclonal antibody that inhibits C5, is used in the treatment of conditions such as paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome.

Related Pages

• Complement system
• Membrane attack complex
• Anaphylatoxin
• Eculizumab