Complement factor I

Complement Factor I

Complement Factor I is a crucial serine protease enzyme in the complement system, which is part of the innate immune system. It plays a vital role in regulating the complement cascade, preventing damage to host tissues by controlling the activation of complement components.

Structure

Complement Factor I is a glycoprotein composed of a single polypeptide chain. It is synthesized primarily in the liver and circulates in the blood plasma. The protein is composed of several domains, including a serine protease domain, which is responsible for its enzymatic activity.

Function

The primary function of Complement Factor I is to cleave and inactivate complement components C3b and C4b. This action is essential for preventing the over-activation of the complement system, which can lead to tissue damage and inflammation. Factor I requires cofactors, such as Factor H, C4b-binding protein, and membrane cofactor protein (MCP), to effectively cleave C3b and C4b.

Regulation of the Complement Pathway

Complement Factor I regulates both the classical pathway and the alternative pathway of the complement system. By cleaving C3b and C4b, Factor I prevents the formation of the C3 and C5 convertases, which are crucial for the amplification of the complement response.

Clinical Significance

Deficiency or dysfunction of Complement Factor I can lead to uncontrolled activation of the complement system, resulting in conditions such as atypical hemolytic uremic syndrome (aHUS), age-related macular degeneration (AMD), and increased susceptibility to infections.

Genetic Mutations

Mutations in the gene encoding Complement Factor I (CFI) can lead to a deficiency in the protein's function. These mutations are often inherited in an autosomal recessive manner, meaning that two copies of the mutated gene are required for the deficiency to manifest.

Diagnostic and Therapeutic Implications

Testing for Complement Factor I levels and activity can be part of the diagnostic workup for patients with suspected complement system disorders. Therapeutic approaches may include the use of complement inhibitors to manage conditions associated with complement dysregulation.

See Also

• Complement system
• Factor H
• C3 convertase
• Serine protease