Identification of a Catalytic Exosite for Complement Component C4 on the Serine Protease Domain of C1s
Author
Summary, in English
The classical pathway of complement is crucial to the immune system, but it also contributes to inflammatory diseases when dys-regulated. Binding of the C1 complex to ligands activates the pathway by inducing autoactivation of associated C1r, after which C1r activates C1s. C1s cleaves complement component C4 and then C2 to cause full activation of the system. The interaction between C1s and C4 involves active site and exosite-mediated events, but the molecular details are unknown. In this study, we identified four positively charged amino acids on the serine protease domain that appear to form a catalytic exosite that is required for efficient cleavage of C4. These residues are coincidentally involved in coordinating a sulfate ion in the crystal structure of the protease. Together with other evidence, this pointed to the involvement of sulfate ions in the interaction with the C4 substrate, and we showed that the protease interacts with a peptide from C4 containing three sulfotyrosine residues. We present a molecular model for the interaction between C1s and C4 that provides support for the above data and poses questions for future research into this aspect of complement activation. The Journal of Immunology, 2012, 189: 2365-2373.
Department/s
Publishing year
2012
Language
English
Pages
2365-2373
Publication/Series
Journal of Immunology
Volume
189
Issue
5
Document type
Journal article
Publisher
American Association of Immunologists
Topic
- Immunology in the medical area
Status
Published
Research group
- Protein Chemistry, Malmö
ISBN/ISSN/Other
- ISSN: 1550-6606