Complement control protein

Overview of complement control proteins in the immune system

Complement control proteins (CCPs) are a group of proteins that regulate the complement system, which is a part of the immune system responsible for enhancing the ability of antibodies and phagocytic cells to clear microbes and damaged cells, promote inflammation, and attack the pathogen's cell membrane. These proteins are crucial in maintaining the balance of the complement system to prevent damage to host tissue.

Structure

Complement control proteins are characterized by the presence of one or more complement control protein domains (CCP domains), also known as short consensus repeats (SCRs) or sushi domains. These domains are typically about 60 amino acids long and are stabilized by two conserved disulfide bonds. The CCP domains are involved in protein-protein interactions that are essential for the regulation of the complement cascade.

Function

The primary function of complement control proteins is to regulate the activation of the complement system to prevent host tissue damage. They achieve this by:

• Inhibiting the formation of the C3 convertase, which is a key enzyme in the complement activation pathways.
• Promoting the decay of C3 convertase once it is formed.
• Facilitating the cleavage and inactivation of complement components such as C3b and C4b.
• Protecting host cells from complement-mediated lysis by binding to complement components and preventing their deposition on host cell surfaces.

Examples

Some well-known complement control proteins include:

• Factor H: A plasma protein that regulates the alternative pathway of complement activation by binding to C3b and promoting its inactivation.
• CD55 (Decay-accelerating factor): A membrane-bound protein that accelerates the decay of C3 convertases on host cell surfaces.
• CD59 (Protectin): A membrane protein that inhibits the formation of the membrane attack complex (MAC) on host cells.
• C4b-binding protein: A plasma protein that regulates the classical and lectin pathways by binding to C4b.

Clinical Significance

Dysregulation of complement control proteins can lead to various diseases. For example, mutations in the gene encoding Factor H are associated with atypical hemolytic uremic syndrome (aHUS) and age-related macular degeneration (AMD). Deficiencies or dysfunctions in complement control proteins can result in increased susceptibility to infections and autoimmune diseases.

Research and Therapeutic Applications

Research into complement control proteins is ongoing, with the aim of developing therapeutic agents that can modulate the complement system. Such therapies could be beneficial in treating diseases where complement dysregulation plays a role, such as systemic lupus erythematosus, rheumatoid arthritis, and certain types of kidney diseases.

Also see

• Complement system
• Immune system
• Autoimmune disease
• Inflammation