Complement Therapeutic Target-C8B

With an accumulation of over ten years of efforts in the biotechnological and pharmacological industry, Creative Biolabs stands up as a global leader which delivers value-added services. We have established brilliant antibody engineering platform, protease inhibitor platform, drug discovery platform and are fully equipped to help global clients with drug discovery and validation based on our knowledge and expertise on complement systems.

Complement Therapeutic Target C8B

The complement mediates responses to inflammatory triggers through a coordinated sequential enzyme cascade leading to the elimination of the pathogen through opsonization and lysis. The pathogen lysis is performed by the membrane attack complex (MAC) which is composed of several complement components, C5, C6, C7, C8, and C9. MAC assembly is initiated by proteolytic cleavage of C5. C8 initiates the membrane penetration and coordinates MAC pore formation. A number of research reports revealed that C8 is a heterotrimer which consists of C8A, C8B, and C8G. C8B is N-glycosylated with one or two bound glycans. The deficiency of C8B leads to the type II of C8 deficiency, leading to the malfunction of MAC.

Fig. 1 Conformational flexibility of membrane attack complex (MAC) pore structure.¹

Function

The MAC induces lysis of susceptible cells and participates in signaling events. When the complement system is initiated, the complement component C3 is transformed into C3a and C3b after several sequential cleavages and activation of other components. C3b binds C3 convertase to form the C5 convertase which initiates the formation of MAC. C5 is cleaved into C5a and C5b. The C5bC6 assembly then binds to C7. The consequential C5b-7 complex binds to C8 which is constituted of three subunits (C8A, C8B, and C8G). C8B participates in at least two binding interactions. It has a high-affinity binding site for C8 alpha chain. C8B also mediates incorporation of C8 into the MAC.

C8B-Related Disease

Complement component 8 deficiency is a disorder that leads to the dysfunction of the complement system and causes the subsequent immunodeficiency. C8B deficiency causes types II of C8 deficiency. This form of C8 deficiency is known as the condition in which the immune system is not able to protect the body effectively from the pathogens. Patients who are suffering from this disorder have a significantly increased susceptibility to developing recurrent infections.

C8B Mutations Leads to the Deficiency

Several mutations in the C8B gene cause complement component 8 deficiency type II. These mutations are most often of a type called a C to T transition, in which a DNA base called cytosine (C) is changed to the nucleotide thymine (T). Moreover, this change occurs in a region of the gene called exon 9, but it can occur in other regions. These mutations alter the sequence of C8B, stopping the translation process in advance and resulting in an abnormally short protein. The “short” C8B impairs the formation of C8 and consequentially leads to the breakdown of MAC.

Creative Biolabs provides high-quality services for drug discovery and validation. Based on the accumulated knowledge and expertise on the complement system, we offer turn-key or ala carte services customized to our client’s needs. If you are interested in our platform or you are calling for our services, please contact us for detailed information.

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References
1. Menny, Anaïs, et al. "CryoEM reveals how the complement membrane attack complex ruptures lipid bilayers." Nature communications 9.1 (2018): 5316.

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• Complement Therapeutic Target-C8G