The conversion of human complement component C5 into fragment C5b by the alternative-pathway C5 convertase

Area of Science:

• Immunology
• Complement System Biology

Background:

• The alternative pathway of the complement system plays a crucial role in innate immunity.
• Understanding the function of complement component C5 convertase is vital for comprehending immune responses.

Purpose of the Study:

• To investigate the cleavage of human complement component C5 by the alternative pathway C5 convertase.
• To elucidate the mechanism and stability of the alternative pathway C5 convertase.

Main Methods:

• Studied the alternative pathway C5 convertase on zymosan, represented as zymosan--C3b2BbP.
• Assessed the decay kinetics of properdin-stabilized C3 and C5 convertase activities.
• Investigated the binding characteristics of C5 and C5b to C3b.

Main Results:

• Alternative pathway C5 convertase activity, stabilized by properdin, has a half-life of 34 minutes, correlating with Bb subunit loss.
• C5 convertase functions stepwise: C5 binds to C3b, followed by C5 cleavage to C5b.
• C5 and C5b exhibit stable C3b binding capacity, unlike C3, C5 does not covalently bond to zymosan or get inhibited by amines, suggesting absence of a thioester group.

Conclusions:

• The alternative pathway C5 convertase mechanism involves sequential C5 binding to C3b and subsequent cleavage.
• The stability of the alternative pathway C5 convertase is dependent on the Bb subunit.
• Human complement component C5 lacks the thioester group found in C3 and C4.