C3 proactivator convertase and its mode of action

Area of Science:

• Biochemistry
• Immunology
• Complement System

Background:

• The complement system plays a crucial role in innate and adaptive immunity.
• Activation of the complement cascade involves a series of protein cleavages and complex formations.
• Understanding the regulatory mechanisms of complement activation is vital for therapeutic interventions.

Purpose of the Study:

• To identify and characterize the factor responsible for converting C3 proactivator (C3PA) to C3 activator in human serum.
• To elucidate the requirements for C3PA conversion by the identified factor.

Main Methods:

• Partial purification of the C3PA converting activity from human serum.
• Biochemical assays to assess the requirements for C3PA conversion.
• Physicochemical and antigenic characterization of C3 fragments.

Main Results:

• The C3PA converting activity was localized to a 3S alpha-globulin, termed C3PA convertase (C3PAse).
• C3PAse activity necessitates metal ions and a C3 fragment resembling C3b.
• Native C3 could not substitute for the C3 fragment in C3PA conversion but could restore hydrazine-treated serum complement activity.
• The C3 fragment, unlike native C3, initiated C3PA conversion in whole serum.

Conclusions:

• A novel enzyme, C3PAse, has been identified and partially purified.
• A C3 fragment, functionally similar to C3b, acts as an effector for C3PAse in C3PA conversion.
• These findings propose a new model for complement activation involving a C3 fragment-mediated feedback loop.