Characterisation of the classical and lectin pathways of complement activation and the roles of complement inhibitors LAIR-2 and BBK32

Abstract

The CP is initiated by a multimeric 790 kDa complex named C1. This complex is formed from a hexameric, bouquet-like protein called C1q assembled from three polypeptide chains A, B and C and four associated serine proteases; two C1r and two C1s, as a Ca2+-dependant heterotetramer. C1r and C1s are homologous modular proteases composed of an N-terminal CUB1 domain, followed by an EGF-like domain, a CUB2 domain followed by two CCP modules, and a serine protease domain (SP). Several models have been proposed to explain how C1 is assembled. In this thesis I have determined the crystal structure of the C1r-C1s complex and propose a detailed model for assembly of C1.