Complement system plays an essential role in host defense and is under strict regulation in the immune responses. With advanced technologies and long-term scientific expertise, Creative Biolabs has explored a series of regulator development services for numerous complement components. Factor H is one important deactivator of complement system. We can offer high-quality and custom services to meet our clients’ demands precisely. Now, we have successfully developed a wide range of complement regulators to control the activation of the complement system.
Introduction of Factor H
Complement system comprises an essential link between the innate and adaptive immune system, and it participates in the elimination of pathogens and altered host cells, maintaining the homeostasis of our body. Factor H (FH) is a soluble glycoprotein that acts as a deactivator of complement system, which is essential for controlling the alternative pathway (AP) in blood and on cell surfaces. Although it can act in the fluid phase, its main role is to bind to host surfaces and protect them against complement activation.
Structure of Factor H
The structure of FH is characterized by 20 complement control protein repeats (CCPs), also known as short consensus repeat domains (SCRs), which are connected by short linkers and arranged in an extended head to tail fashion. SCR domains are compact all-β elliptical structures stabilized by two disulfide bridges. CCP 1-4 is responsible for the cofactor and decay acceleration activities of FH. In addition, it is documented that the carboxyl-terminal domains CCP 19-20 interact with the major opsonin C3b, glycosaminoglycans, and endothelial cells, and even be utilized by pathogenic microbes for complement evasion.
Fig. 1 Complement H tetramer in human.1
Functions of Factor H
As the key regulator of AP in plasma, FH regulates AP activation by competing with factor B in binding to C3b, by acting as a cofactor for factor I to proteolytically inactivate C3b, and by enhancing dissociation of the C3bBb complex (C3 convertase) and the C3bBb3b complex (C5 convertase). Notably, FH is practically the only regulator that downregulates AP activation on host structures that lack the membrane-bound regulators, such as basement membranes in kidney glomeruli. It is interesting that FH can be recruited to host membranes by recognizing and binding self-components, such as glycosaminoglycans, preventing opsonization of host tissue with low expression of surface regulators of complement activation (RCAs), and protecting host cells from self-attack by complement. Several pathogenic microorganisms evade the attack of the complement system by expressing structural homologs of FH or recruiting host FH to their surfaces via FH-binding proteins.
Fig.2 Function of FH in the alternative complement pathway. (Atkinson, 2007)
Clinical Significance of Factor H
Due to the central role in maintaining a well-balanced complement activation and immune response, FH is associated with a number of clinical implications, such as:
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Age-related Macular Degeneration (AMD)
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Schizophrenia
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Ischemic Stroke
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Atypical Hemolytic Uremic Syndrome (aHUS)
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Membranoproliferative Glomerulonephritis Type II (MPGN-II)
FH deficiency will induce increased complement activity on healthy host cells, resulting in autoimmune diseases. Any mutation or single nucleotide polymorphisms (SNPs) in FH may lead to pathologies. Moreover, the complement inhibitory activity of FH is often used by pathogens to increase virulence.
Owing to the vital roles in complement activation and immune modulation, therapeutic targeting of FH is considered important for the treatment of diseases associated with abnormal or loss of complement control. FH has become a promising and effective target for therapeutic antibody exploration and clinical trial.
Why Choose Us?
Creative Biolabs can offer a full range of formulation development services for complement products and therapeutic drug exploration to meet our clients’ demands precisely.
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Industry leadership
Our industry-leading expertise in the biopharma research and scalable formulation can help you promote your therapeutics and medical projects.
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Professional team
Our scientists are specialized in the regulatory knowledge and scientific applications specific to drug development.
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Abundant experience
We have successfully completed a lot of drug discovery
For more information about our complement services, please contact us now.
References
1. From Wikipedia: Deposition authors: Jaakola, V.-P., Jokiranta, T.S., Goldman, A.; visualization author: User:Astrojan - CC BY-SA 4.0, https://commons.wikimedia.org/wiki/File:2g7i.jpg
2. Atkinson, John P., and Timothy HJ Goodship. "Complement factor H and the hemolytic uremic syndrome." The Journal of experimental medicine 204.6 (2007): 1245-1248
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