Background
The complement is an intricate system of serum proteins that mediates innate humoral immunity through a complement cascade procedure, ultimately lead to accomplishing its biologic roles in inflammation. Complement component C5 is one of the central pillars of this system and plays a major role in host defense. A panel of complement proteins is activated sequential order during steps of the cascade to produce a variety of molecules that maintain homeostasis. Upon the formation of C5 convertases via the classical or alternative pathways of complement activation, which are an essential protease formed during the upstream activation process and further cleave C5 into fragments of C5a and C5b. C5b initiates the assembly of the membrane attack complex (MAC), and this complex culminates in the pore formation of pathogenic membranes that lead to cell lysis and death.
Fig. 1 The 3D model of human C5.1
Component C5a and C5b
C5 is the fifth component of the complement system, which plays a central role in inflammatory and cell killing processes. The complement C5 protein is an initiator of the effector terminal phase of the complement system and the molecular structure consists of the C5 alpha and C5 beta chains, which are linked by a disulfide bridge. Cleavage of the C5 by C5 convertase results in the formation of the small C5a fragment and the large C5b fragment.
C5a is the most potent type of proinflammatory anaphylatoxins generated during complement activation. C5a is a chemoattractant for leukocytes in stimulating an inflammatory response targeting a broad spectrum of immune and nonimmune cells and the excessive or uncontrolled production of C5a occurs in a number of inflammatory diseases. The C5b macromolecular cleavage product forms a complex with the C6 complement component, and this complex initiates the assembly of the C5 to C9 components into the MAC, which leads to cell lysis and death. C5a elicits a variety of biological effects that are essential in the clearance of pathogens and for host defense, including increased vascular permeability, chemotaxis of inflammatory cells, respiratory burst, cytokine and chemokine release and phagocytosis.
Fig.2 The generation of C5a and C5b. (Horiuchi, 2016)
Complement Component C5 Based Therapy
C5 appears to be an attractive therapeutic target to control because of the release of the potent proinflammatory peptide C5a and to the assembly of the terminal C complex responsible for tissue damage and inflammation to fight infection, clear immunocomplexes and maintain self-tolerance. Various types of antibodies and compounds such as peptides or non-peptides have actively been developed, and these substances act as inhibitors of complement components C5 and C5a and antagonists of the C5a receptor, which selectively allows inhibition of the C5b and C5a-mediated responses while leaving the rest of complement unaffected. These C5 and C5a receptor antagonists may be efficacious at treating various inflammatory diseases involving complements.
With the first complement inhibitors Eculizumab, a humanized monoclonal antibody against complement component C5 approved by the US Food and Drug Administration (FDA), the complement C5 has emerged as an attractive therapeutic target and has advanced into the spotlight of drug discovery to facilitate the clinical development of other promising drug candidates. Besides, the C5aR, a G-protein-coupled signaling receptor, is one of the C5a binding receptors and has been identified as an attractive drug target for a long time. Creative Biolabs offers anti-C5 antibodies, recombinant C5 proteins, C5 ELISA kits, C5 blocking peptides, C5 drug development to support your drug discovery project.
If you are interested in more information, please do not hesitate to contact us for more details.
References
-
From Wikipedia: By Pietro Roversi - Made from PDB ID 3CU7 by author, https://commons.wikimedia.org/wiki/File:C5.png
-
Horiuchi, Takahiko, and Hiroshi Tsukamoto. "Complement-targeted therapy: development of C5-and C5a-targeted inhibition." Inflammation and regeneration 36.1 (2016): 1-5.
Related Product
For Research Use Only.
Related Sections:
