C1 Complex: An Adaptable Proteolytic Module for Complement and Non-Complement Functions

C1 Complex: An Adaptable Proteolytic Module for Complement and Non-Complement Functions

Complement C1 is the defining component of the classical pathway. Within the C1qC1r2C1s2 complex, C1q functions as a molecular scaffold for C1r2C1s2 and C1q binding to its ligands activates these two serine proteases. The classic C1q ligands are antigen-bound antibodies and activated C1s cleaves C4 and C2 to initiate the complement cascade. Recent studies suggest broad C1 functions beyond the c...

Structure of the C1 complex of complement.

In PNAS, Mortensen et al. (1) propose a model of the C1 complex of complement derived from small-angle X-ray scattering (SAXS) and electron microscopy (EM) analyses that contradicts previously published models and suggests an intermolecular activation process. This proposal is largely derived from a conjectural structure of C1r2C1s2, the catalytic unit of C1, in which the serine protease (SP) d...

Inhibition of Immune Complex Complement Activation and Neutrophil Extracellular Trap Formation by Peptide Inhibitor of Complement C1

Two major aspects of systemic lupus erythematosus (SLE) pathogenesis that have yet to be targeted therapeutically are immune complex-initiated complement activation and neutrophil extracellular trap (NET) formation by neutrophils. Here, we report in vitro testing of peptide inhibitor of complement C1 (PIC1) in assays of immune complexmediated complement activation in human sera and assays for N...

The proteolytic enzymes of the complement system.

Peptide Inhibitor of Complement C1 (PIC1) Rapidly Inhibits Complement Activation after Intravascular Injection in Rats

The complement system has been increasingly recognized to play a pivotal role in a variety of inflammatory and autoimmune diseases. Consequently, therapeutic modulators of the classical, lectin and alternative pathways of the complement system are currently in pre-clinical and clinical development. Our laboratory has identified a peptide that specifically inhibits the classical and lectin pathw...