Creative Biolabs is an innovative and ambitious company which delivers value-added services. We have established brilliant antibody engineering platform, protease inhibitor platform, and drug discovery platform and are fully equipped to partner with our clients who are working on complement systems for drug discovery and validation.
Complement Therapeutic Target C8
As the guardian of our body, the immune system is eliminating the pathogen or invaders constantly. The immune system is classified into two parts: innate immune system and adaptive immune system. Unlike the adaptive immune responses, the innate immune responses are not long-lasting immunity against the pathogen and they are found in all classes of life such as plants and animals.
The complement system is playing a pivotal role in the innate immune response and the key step is the formation of the membrane attack complex (MAC). Complement component C8 is an important part of MAC. C8 initiates the membrane penetration and coordinates MAC pore formation. Electron microscopy revealed that C8 is a heterotrimer which has a three-chain structure organized in two subunits, C8α-γ and C8β. The deficiency of C8 causes the dysfunction of the complement system, resulting in the ineffectiveness of eliminating the pathogen.
Fig.1 Structure of C8. A, ribbon model showing C8α (red), C8β (blue), and C8γ (green). MACPF domains are in dark colors and modules in light colors. B, view of C8α oriented as in A. (Lovelace, et al., 2011)
Function
The MAC is responsible for the lysis of the invading pathogens. Initially, the pathogens are sensed and the complement system is triggered. All the signals of the complement cascades converge on the complement component C3 which is cleaved into C3a and C3b. Furthermore, C3b forms a complex called C5 convertase.
C5 convertase transforms C5 into C5a and C5b. The C5bC6 assembly then binds to C7, a membrane anchor, and the resulting complex binds to C8 which is composed of three subunits (C8A, C8B, and C8G). The C8B mediates the interaction of C8 with the C5b-7 complex. C9 associates through the interaction with a C9 specific site on the α-chain.
C8-Related Disease
There are two subtypes of C8 deficiency, types I and II, classified by their genetic cause. These two types have the same signs and symptoms.
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C8 deficiency type I
Patients with C8 deficiency type I suffer from recurrent infection, predominantly with Meningococcal Meningitis. Most patients are discovered to capture such disorder when they had their first episode of meningitis at the age of about 10 years old.
Associated gene: C8A
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C8 deficiency type II
Patients with C8 deficiency type II have the similar symptoms to C8 deficiency type I. These two types are clinically indistinguishable.
Associated gene: C8B, C8G
Complement deficiency is associated with autoimmune disorders and increased susceptibility to certain infections. Creative Biolabs' outstanding research team are providing high-quality biotherapeutics development services on the complement-related drug discovery and validation. 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
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Lovelace, L. L.; et al. Structure of human C8 protein provides mechanistic insight into membrane pore formation by complement. Journal of Biological Chemistry. 2011, 286(20), 17585-17592.
Questions & Answer
A: Current research in understanding the structure-function relationship of C8 involves structural biology techniques, such as X-ray crystallography and cryo-electron microscopy, to determine the 3D structure of C8 and its interactions with other complement proteins. This knowledge can inform the design of novel drugs targeting C8 with improved specificity and efficacy.
A: Complement components, such as C5, C8, and C9, play distinct but interconnected roles in the complement system. While C5 is primarily responsible for initiating the formation of the MAC, C8 plays a crucial role in the middle stages of MAC assembly, acting as a bridge between C5b-7 and C9. Therapeutically, targeting C8 may offer a more specific intervention point compared to C5 or C9, depending on the disease being treated.
A: Innovative research strategies aim to develop bispecific antibodies that simultaneously target C8 and other complement components to disrupt MAC assembly. Additionally, the use of gene editing techniques, like CRISPR-Cas9, to modify the expression or function of C8 genes in specific disease contexts holds promise for precision medicine.
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