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Complement proteins C3b, C4b, and membrane attack complex (C5b-9) (C3b, C4b, MAC (C5b-9 complex))

Target
C3b, C4b, MAC (C5b-9 complex)
Molecular classification
Enzyme cleaved fragments (C3b, C4b), Complement complex (membrane attack complex), Other (multi-protein immune effector complex)
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Overview

The complement proteins C3b and C4b are central fragments generated in all complement pathways after activation and play crucial roles in tagging (opsonizing) pathogens and facilitating immune complex clearance by interacting with specific cell surface complement receptors on phagocytes. The fragments serve as subunits for enzymatic convertases that drive further pathway activation, including the formation of the C5 convertase, which cleaves C5 to generate C5b. C5b initiates assembly of the terminal complement complex, commonly known as the membrane attack complex (MAC, C5b-9), a multi-subunit ring that forms transmembrane pores leading to cell lysis. The MAC is responsible for direct killing of pathogens, but excessive activation can injure host tissues, implicating these proteins and complexes in inflammatory, autoimmune, cardiovascular, and neurodegenerative diseases. Therapeutics targeting components of this cascade are in clinical use for conditions with complement-mediated tissue damage. For structured databases or therapeutic drug targeting, C3b, C4b, and C5b-9 complex (MAC) should be separated. "C3b/C4b/C5b-9 complex" as a single entity is not standard nomenclature, and may cause ambiguity in downstream data use.

Other names
C3bC4bMAC (for membrane attack complex, C5b-9)Terminal complement complexC3b fragmentC4b fragmentC5b-C9 complex
02

Mechanism of action

Inhibition of complement activation at C5 (prevents MAC formation); Inhibition of C3/C4 cleavage or opsonization (blocks immune activation); Blockade of receptor-mediated downstream signaling (e.g., C5a receptor inhibition)

03

Biological functions

Opsonization and phagocytosis (C3b, C4b)Formation of membrane attack complex and cell lysis (C5b-9)Inflammation (via anaphylatoxins and downstream products)Immune complex clearanceActivation of adaptive immunity through B cell co-receptor signaling (C3d fragment)Tissue regeneration and repair (via C3a, C5a signaling)
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Disease associations

InflammationAutoimmune diseaseCardiovascular diseaseInfectionNeurodegenerative diseaseCancer (less established, but complement activation implicated)
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Safety considerations

Increased risk of infections, especially encapsulated bacteria (e.g., Neisseria meningitidis), due to impaired terminal complement activityAutoimmune phenomena from excessive complement inhibitionOff-target inflammatory effectsHypersensitivity or infusion reactions
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Interacting drugs

Eculizumab

4 more in the full profile.

07

Biomarkers

Levels of C3b, C4b, and circulating MAC (C5b-9)Split product fragments (C3a, C5a)Plasma membrane deposition of MAC (as marker of complement activation)Soluble MAC (sC5b-9) for therapy monitoring

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