C5-convertase

C5 convertase is an enzyme belonging to a family of serine proteases that play key role in the innate immunity.

The formation of the alternative pathway C5 convertase (C3bBbC3b) starts by spontaneous cleavage of C3 protein exposing previously hidden thioester bond.

However, when C3b undergoes its post-cleavage conformational change, a binding site for a plasma protein called Factor B is also exposed.

This comparatively low level of stabilizing disulfide bridges may provide a partial explanation for the irreversible conformational change imparted on C5 after cleavage to C5a and C5b.

In addition, the relatively low number of disulfide bonds could account for instability of C5 when exposed to chaotropic agents such as potassium thiocyanate.

Research has shown that during the classical pathway of the complement system, an inactive A6 allotype of c4 completely stalls the molecules' ability to act as a c5 binding subunit1.

The proteolytic cleavage of C5 is the only known enzymatic event in assembly of the cytolytic membrane attack complex of complement.

The extent of formation of the C5 intermediate complex is primarily dependent on the number of molecules of C4, C2 and C3 present on the cells employed for its generation.

In addition, the hemolytic activity of the isolated C5 intermediate complex is exceedingly labile, having an average half-life at 30 °C of only 9 rain.

However, unlike C2, C5 remains firmly cell-bound during the decay process and apparently undergoes an alteration in situ which renders it hemolyticly unreactive.

This nonspecifically bound C5 remains firmly attached, although it may be specifically utilized as a source of C5 by an ongoing complement reaction.

FHR1 blocks C5 convertase activity and interferes with C5b surface deposition and membrane attack complex (MAC) formation.