[Biochemical data on C1 intrinsic activation (author's transl)].

Area of Science:

• Biochemistry and Molecular Biology
• Immunology

Context:

• The complement system's C1 complex initiates the classical pathway, crucial for immune responses.
• Understanding C1 activation is key to modulating immune complex clearance and inflammation.

Purpose:

• To elucidate the distinct mechanisms governing the activation of the C1 complex.
• To characterize the autocatalytic processes involved in C1r activation.
• To investigate the differential effects of inhibitors on C1 activation pathways.

Summary:

• C1 activation involves the proteolytic cleavage of C1r, generating enzymatic activity.
• Two coexisting mechanisms of C1r activation were identified: intradimer and interdimer proteolysis.
• DFP and C1-inhibitor selectively blocked the interdimer activation pathway.

Impact:

• Provides a detailed mechanistic understanding of C1 activation.
• Suggests potential targets for therapeutic intervention in complement-mediated diseases.
• Contributes to a proposed model of C1 activation based on biochemical and structural data.