Overview of Complement Component Factor Properdin/CFP
Introduction of complement factor P, a 53 kDa glycoprotein, is composed of six thrombospondin type 1 repeat domains (TSR1-6) and a truncated N-terminal domain (TSR0). The monomer is 26 nm in length x 2.5 nm in diameter and consists of 442 amino acid residues. It contains an N-glycosylation site in TSR-6 and is C-mannosylated at 14 different tryptophans. The flexible monomeric subunits associate head-to-tail into mainly cyclic dimers, trimers, or tetramers with curly vertex structures. Under physiological conditions, the properdin monomers form cyclic dimers, trimers and tetramers at a ratio of about 1: 2: 1.
Fig.1 Structure of CFP. (Blatt, 2016)
CFP is the only known positive regulator of complement activation by stabilizing the alternative pathway convertase through C3 binding, thus increasing the half-life of the C3 and C5 convertases. Properdin is also an initiator of the alternative pathway. Unlike most complement components that are produced by the liver, properdin is primarily synthesized by leukocytes, including T cells, monocytes, and mast cells. The protein is also stored in the secondary granules of neutrophils from which it is released upon stimulation. The properdin gene is located on the X chromosome and deficiency leads to impaired alternative pathway function, making patients extremely vulnerable to fulminant meningococcal infections. Moreover, properdin plays a central role in animal models of various Complement therapeutics for inflammatory diseases.
The Function of CFP
Properdin is the only positive regulator of the complement system. It promotes the activity of this defense system by stabilizing the convertases of the complement alternative pathway. Properdin enhances the activity of the alternative pathway: (1) acting as a positive regulator of pre-existing alternative pathway activity or (2) initiating alternative pathway activity. It acts as a positive regulator by stabilizing the alternative pathway C3 and C5 convertases, increasing their activity 5- to 10-fold. Recent in vitro studies suggest that properdin may serve as a specific pattern recognition molecule. As a pattern recognition molecule, properdin binds selectively to specific surfaces on which C3b or C3(H2O) is recruited to initiate alternative pathway activity.
Fig.1 Properdin functions. (Blatt, 2016)
Clinical Significance of CFP
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CFP deficiency
CFP deficiency is an X-linked disorder, which is one of the most common complement deficiencies in whites. It is closely related to the increased meningitis susceptibility. More than 100 cases have been recorded in 25 over families. Compared to normal individuals, meningococcal infections in CFP-deficient patients have higher mortality. In addition to increasing the risk of meningococcal infections, CFP deficiency is also associated with the recurrence of otitis media and pneumonia. These findings highlight the importance of properdin in the host's defenses against some, but not necessarily all, pathogens.
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Potential role for CFP in human pathologies
The involvement of CFP in other human diseases has only recently been elucidated. In the past few years, there have been several studies on complement-related diseases, which have found changes in the levels of systemic properdin. These studies suggest that changes in properdin levels may play an important role in these diseases.
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The role of properdin in complement-mediated renal injury
Disrupting the balance between activation and regulation of alternative pathways is related to the occurrence of many diseases. The glomerulus is particularly vulnerable to complement attack. Properdin is a positive regulator of alternative pathways and has been implicated in the development of complement-related kidney disease, including C3G and aHUS. For example, C3G is a serious complement-mediated renal disease, and up to 50% of patients progress to end-stage renal disease. C3G occurs due to glomerular damage caused by excessive activation of alternative pathways. Properdin can stabilize C3 convertase of alternative pathways and has a complement regulatory role, so it can prevent overactivity of alternative pathways and subsequent damage.
Creative Biolabs offers a full range of complement component CFP related products, including:
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CFP Antibodies
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CFP Related Array Kits
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CFP Related Peptides
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CFP Related Lysates
If you want more information, please feel free to contact us.
Related Product
Reference
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Blatt, A. Z.; et al. Properdin: a tightly regulated critical inflammatory modulator. Immunological reviews. 2016, 274(1): 172-190.
For Research Use Only.
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