Complement C5 is part of the terminal sequence in the complement pathway. In particular, it is cleaved into C5a and C5b which are responsible for chemotaxis, inflammation, and initiating the formation of the membrane attack complex (MAC). Drugs that inhibit complement C5 have been used in Paroxysmal nocturnal hemoglobinuria (PNH) patients to lessen thrombotic complications by lessening intravascular hemolysis.
Native, human C5 complement component. Glycoprotein composed of two non-identical subunits of M.W. 120 kDa (α) and 75 kDa (β) linked by disulfide bonds. Present in normal human serum at 70 μg/ml. Activation of complement via either the classical or alternative pathway can result in the assembly of C5-cleaving enzymes (C5 convertases) on target surfaces. Both C5 convertases cleave the C5 α-chain at peptide bond 74 resulting in production of C5a (M.W. 11,200) and C5b fragments (M.W. 185,000). Released C5a peptide is one of the three complement-derived anaphylatoxins. C5b fragment combines with C6, C7, C8, and C9 to form lytic C5b-9 complement membrane attack complex (MAC).
Complement component C5 is processed by convertase enzymes in a cascade modulated in a unique way. The multi-subunit catalytic complex initially shows little activity against C5, but instead cleaves C3. A C3 cleavage product C3b covalently attaches to the complex and shifts its specificity to C5 by a factor of 1000.
