Molecular determinants of the substrate specificity of the complement-initiating protease, C1r.

ABSTRACT: The serine protease, C1r, initiates activation of the classical pathway of complement, which is a crucial innate defense mechanism against pathogens and altered-self cells. C1r both autoactivates and subsequently cleaves and activates C1s. Because complement is implicated in many inflammatory diseases, an understanding of the interaction between C1r and its target substrates is required for the design of effective inhibitors of complement activation. Examination of the active site specificity of C1r using phage library technology revealed clear specificity for Gln at P2 and Ile at P1', which are found in these positions in physiological substrates of C1r. Removal of one or both of the Gln at P2 and Ile at P1' in the C1s substrate reduced the rate of C1r activation. Substituting a Gln resid

SUBMITTER: Wijeyewickrema LC 

PROVIDER: S-EPMC3668718 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature