C4b Binding Protein

Background

C4b binding protein (C4BP) is a 540 kDa plasma glycoprotein synthesized in the liver, presenting in circulation at a concentration of ~200 mg/L. Human C4BP is a protein complex composed of six/seven identical α chains and a β single chain, named as C4BPA and C4BPB, respectively. Both α chain and β chain contain two cysteine residues and an amphipathic α-helix, which are attached by disulfide bonds forming a unique spider-like structure. Each α chain contains eight complement control protein (CCP) repeat domains and a binding site for the activated complement C4b, whereas, the β chain contains three CCP domains and a protein S binding site.

In the complement system, C4BP functions as a soluble inhibitor of the complement classical pathway and complement lectin pathway. Firstly, C4BP serves as a cofactor to the complement factor I (a regulatory enzyme inhibiting complement activation), in which the complement C4b bind to the α chains of the C4BP (CCP1-3 domains) and is immediately inactivated. Secondly, C4BP accelerates the decay of the unstable C3 convertase (C4bC2a), and binds to complement C3b preventing the assembly of the C5 convertase. Thirdly, C4BP also interacts with other ligands, such as vitamin K-dependent anticoagulant protein S (via the β chain), heparin, C-reactive protein, and some bacterial proteins. It has been reported that C4BP deficiency or mutation was involved in atypical hemolytic uremic syndrome (aHUS) and recurrent pregnancy loss.

Fig.1 C4BP structure.^{1, 3}

C4BP Functional Service

Creative Biolabs offers an extensive array of products related to C4BP, such as anti-C4BP antibodies, ELISA kits, and recombinant C4BP proteins. These offerings are adeptly designed to facilitate the detection and monitoring of interactions between complement factors and C4BP proteins. These regents are crucial in propelling forward research efforts targeted at crafting therapeutic solutions for a variety of ailments.

Fig.2 Interaction of surface-linked C4BP with various influenza a virus subtypes.^{2, 3}

C4BP, a principal inhibitor of the classical and lectin pathways in the complement system, may exert complement-independent action against pathogens. Researchers explored C4BP’s binding affinity to Influenza A Virus (IAV) subtypes using indirect ELISA, revealing that C4BP attaches to H1N1 and H3N2 via sites in Complement Control Protein (CCP) 1. Binding was stronger to H3N2 than H1N1. C4BP associated with envelope proteins Haemagglutinin, Neuraminidase, and Matrix protein 1, inhibiting H1N1 infection in lung epithelial cell, yet facilitating H3N2. This suggests C4BP modulates IAV entry and replication differently, potentially offering defense beyond complement regulation.

Creative Biolabs presents an extensive portfolio of functional service offerings centered around C4BP, comprising detailed interaction analyses and a variety of specialized assessments. These meticulously customized services aim to support clients in advancing their scientific research and clinical initiatives.

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References

1. Breda, Leandro CD, et al. "Fine mapping of the interaction between C4b-binding protein and outer membrane proteins LigA and LigB of pathogenic Leptospira interrogans." PLoS neglected tropical diseases 9.10 (2015): e0004192.
2. Varghese, Praveen M., et al. "C4b binding protein acts as an innate immune effector against influenza A virus." Frontiers in Immunology 11 (2021): 585361.
3. Distributed under Open Access license CC BY 4.0, without modification.