Complement C1R

Complement C1r, a modular serine protease in the serum C1 complex, forms a homodimer of 173 kDa. It has two N-terminal CUB domains, separated by an epidermal growth factor (EGF)-like domain, followed by two complement control modules (CCPs) and a C-terminal serine protease (SP) domain. C1r is mainly related to the homologous C1s protease in a calcium-dependent manner. Moreover, the expression of the C1r and C1s proteases is coordinated in hepatocytes. The main function of them is the activation of the classical complement pathway. When the C1 complex binds to an activating target, the C1r is activated, which is induced by the cleavage of a single Arg-Ile bond, which triggers a conformational transition towards the active state.

Until now, structures of the C1r catalytic domain have been determined in both the proenzyme and activated states. To date, C1r complete deficiencies are rare and often associated with pyogenic infections and autoimmune diseases such as systemic lupus erythematosus. Some heterozygous C1r mutations are associated with periodontal Ehlers-Danlos syndrome. Besides, scientists have demonstrated that enhanced expression of C1 complex proteases is related to increased tissue inflammation and complement C3 formation and represents an important pathogenic mechanism leading to FA-mediated tubulointerstitial fibrosis.

Reference

1. Zhang, Wenjie, Yuan Chen, and Hui Pei. "C1q and central nervous system disorders." Frontiers in Immunology 14 (2023): 1145649.