Factor D

Background

The complement activation, amplification, and progression are strictly regulated by a series of factors and proteins. Complement factor D (CFD) is an indispensable regulator of the alternative pathway of complement activation.

CFD, also known as adipsin, is a serine protease synthesized by the liver and adipocytes. Human CFD is a non-glycosylated single polypeptide chain with two variants, a 253-amino acid variant 1 and a 260-amino acid variant 2. The structure of CFD is characterized by two antiparallel β-barrel domains, which are quite similar to other serine proteases. CFD differs from other serine proteases in that there are several unique amino acid substitutions, leading to significant changes in the catalytic domain and substrate-specific loops. Human CFD circulates in the plasma in a deactivated state until it binds to substrate and undergoes conformation change.

In the activation of the complement alternative pathway, CFD cleaves its unique substrate, C3b (or C3(H₂O)) bound complement factor B (CFB), between Arg233 and Lys234. The cleavage generates the alternative pathway C3 convertases C3bBb (or C3(H₂O)Bb). Thus, CFD, serving as a key and rate-limiting component in the alternative pathway cascade. Additionally, it has been indicated that CFD also plays an unexpected role in triglyceride synthesis in adipose tissue and energy balance regulation. Human CFD deficiency can cause an increased risk of infections, especially in Neisseria infections. CFD inhibitor has been developed for the treatment of disorders caused by complement over-activation, such as paroxysmal nocturnal hemoglobinuria (PNH).

Fig.1 The functions of complement Factor D in the alternative complement pathway. Distributed under CC BY-SA 3.0, from Wiki, without modification.

Factor D Functional Service

Creative Biolabs provides a comprehensive range of Factor D-related products, encompassing anti-Factor D monoclonal/polyclonal Antibodies, complement Factor D ELISA Assay Kits, and complement Factor D Proteins. These products are invaluable tools for researchers investigating the complex role of Factor D in immune responses, inflammation, and various disease conditions.

Fig.2 Factor D and the alternative complement in health and disease.¹

Factor D functionality typically involves assessing its role in the alternative pathway of the complement system utilizing the above products. Anti-Factor D antibodies can be used in WB, ELISA, IP, etc., to assess Factor D expression. ELISA kits can measure Factor D protein levels in various biological samples to effectively deduce the operational dynamics of Factor D. Inhibition of Factor D enzymatic activity can be evaluated with purified human Factor D and its natural substrate C3bB. Functional hemolytic tests for Factor D can evaluate the impact of Factor D inhibitors or genetic variants on complement activation. Additionally, Factor D inhibitors are utilized to explore potential therapeutic approaches in complement-related pathologies. Studies have shown that inhibiting Factor D can reduce excessive complement activation, providing a potential treatment for conditions like age-related macular degeneration and PNH.

Creative Biolabs provides Factor D-functional services, including Factor D binding test, Factor D enzymatic activity test, hemolysis test, etc. Our team of experts offers tailored support for researchers and can assist with experimental design, data analysis, and interpretation, ensuring the success of your research projects.

Reference

1. Barratt, Jonathan, and Ilene Weitz. "Complement factor D as a strategic target for regulating the alternative complement pathway." Frontiers in immunology 12 (2021): 712572. Distributed under Open Access license CC BY 4.0, without modification.