Structure of the C1r-C1s interaction of the C1 complex of complement activation.

ABSTRACT: The multiprotein complex C1 initiates the classical pathway of complement activation on binding to antibody-antigen complexes, pathogen surfaces, apoptotic cells, and polyanionic structures. It is formed from the recognition subcomponent C1q and a tetramer of proteases C1r₂C1s₂ as a Ca²⁺-dependent complex. Here we have determined the structure of a complex between the CUB1-EGF-CUB2 fragments of C1r and C1s to reveal the C1r-C1s interaction that forms the core of C1. Both fragments are L-shaped and interlock to form a compact antiparallel heterodimer with a Ca²⁺ from each subcomponent at the interface. Contacts, involving all three domains of each protease, are more extensive than those of C1r or C1s homodimers, explaining why heterocomplexes form

SUBMITTER: Almitairi JOM 

PROVIDER: S-EPMC5789954 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature