Complement Component C5b

Complement component C5b is a vital element of the innate immune system, playing a pivotal role in the body's defense against pathogens and altered self-cells. As a key component of the complement cascade, C5b initiates the formation of the membrane attack complex (MAC), a powerful weapon in the immune system's arsenal.

Structure of C5b

C5b is derived from its precursor, complement component C5, a large protein with a molecular weight of approximately 185,000 Da. C5 is composed of two chains, α and β, linked by a disulfide bond. The formation of C5b occurs through the cleavage of C5 by C5 convertase, a process that results in two fragments:

• C5a: A small anaphylatoxin (74 residues) excised from the center of the molecule.
• C5b: The larger fragment that initiates MAC formation.

This cleavage event triggers significant conformational changes in C5b, similar to those observed in the homologous C3b, but with several important distinctions.

Fig. 1 Structural differences between C5b and C5.^1,2

After cleavage, C5b retains most of the structural elements of C5, including:

• The MG scaffold
• Link domain
• CUB domain
• C5d domain
• Thioester-containing domain (TED)

The conversion from C5 to C5b involves substantial rearrangements of these domains, particularly in the C-terminal region. Immediately after formation, C5b rapidly associates with complement component C6 to form a stable C5b-6 complex.

Fig. 2 Molecular surface representation of C5b-6.^1,2

Functional Roles of C5b in Immunity

C5b plays several crucial roles in the immune system, particularly as a key component of the complement cascade. Its primary functions include:

Table 1 Functional of C5b in immunity.

Understanding these diverse functions of C5b is crucial for developing targeted therapies for complement-mediated disorders and exploring its potential roles in various pathological conditions. The potent effects of C5b and MAC need to be tightly regulated to prevent damage to host tissues. Several regulatory mechanisms exist.

• Membrane-bound regulators: CD59 and other proteins on host cell surfaces inhibit MAC formation.
• Fluid-phase regulators: Proteins such as vitronectin and clusterin can bind to nascent C5b-6 complexes, preventing their insertion into membranes.
• Time-dependent inactivation: C5b has a limited half-life in its active form, spontaneously losing its ability to initiate MAC formation if not rapidly bound by C6.

Complement C5b Test

The complement C5b functional test is designed to measure the activity of C5b in the immune system. The test is based on detecting the activation of complement components and the formation of C5b and MAC. The method involves isolating plasma or serum samples and using hemolytic assays, ELISA, or similar immunoassays to detect and measure C5b levels.

Creative Biolabs provides first-class and personalized complement C5b functional test services tailored to your research needs. Our advanced techniques and expertise ensure precise and reliable quantification of C5b activity.

C5b ELISA

Hemolysis Assay

Functional tests for C5b are extensively used in research.

• Experimental models: ELISA-based assays are optimized for animal models like rats to study conditions such as renal ischemia/reperfusion injury. These models help elucidate the role of terminal pathway activation in various diseases.
• Therapeutic development: These methods provide data on drug binding affinity, specificity, and mechanism of action.

C5b and Disease Pathology

C5b plays a significant role in various pathological conditions, primarily through its involvement in the formation of the MAC.

Table 2 Key pathological roles of C5b.

C5b as a Therapeutic Target

C5b, a key player in the formation of the MAC, has emerged as an important therapeutic target due to its role in complement-mediated diseases. Therapeutic strategies aimed at C5b focus on inhibiting its formation, blocking MAC assembly, or modulating downstream effects.

• Monoclonal antibodies targeting C5
  The most established therapeutic approach involves monoclonal antibodies that inhibit the cleavage of C5 into C5a and C5b.
• Small-molecule inhibitors
  These inhibitors are designed to interfere with specific interactions required for MAC assembly, such as the binding of C5b to C6 or subsequent components.
• Peptidomimetics
  These compounds can block interactions between C5b and other MAC components, such as C6 or C7.
• Complement regulatory protein engineering
  Therapeutic strategies include engineering proteins that enhance natural complement regulation.
• Gene therapy approaches
  Emerging gene-editing technologies offer potential for long-term modulation of complement activity.
• Targeting downstream effects
  In addition to blocking MAC formation, some therapies aim to mitigate the downstream effects of complement activation.

Creative Biolabs is a global leader in biotechnology solutions, specializing in antibody development, protein engineering and therapeutic discovery. For customized solutions for complement system research, please contact our team of experts.

• Complement C5b Functional Test
• Antibodies
• Sera and Plasmas
• Proteins
• Reagents

References

1. Aleshin, Alexander E., et al. "Crystal structure of C5b-6 suggests structural basis for priming assembly of the membrane attack complex." Journal of Biological Chemistry 287.23 (2012): 19642-19652. https://doi.org/10.1074/jbc.M112.361121
2. under Open Access license CC BY 4.0, without modification.

• Complement Component C5a