Projects per year
The structure of the complement-binding domain of Staphylococcus aureus protein Sbi (Sbi-IV) in complex with ligand C3d is presented. The 1.7 angstrom resolution structure reveals the molecular details of the recognition of thioester-containing fragment C3d of the central complement component C3, involving interactions between residues of Sbi-IV helix alpha 2 and the acidic concave surface of C3d. The complex provides a structural basis for the binding preference of Sbi for native C3 over C3b and explains how Sbi-IV inhibits the interaction between C3d and complement receptor 2. A second C3d binding site on Sbi-IV is identified in the crystal structure that is not observed in related S. aureus C3 inhibitors Efb-C and Ehp. This binding mode perhaps hints as to how Sbi-IV, as part of Sbi, forms a C3b-Sbi adduct and causes futile consumption of C3, an extraordinary aspect of Sbi function that is not shared by any other known Staphylococcal complement inhibitor.
1/11/07 → 28/02/09
Project: Research council
Clark, E. A., Crennell, S., Upadhyay, A., Zozulya, A. V., Mackay, J. D., Svergun, D. I., Bagby, S., & van den Elsen, J. M. H. (2011). A structural basis for Staphylococcal complement subversion: X-ray structure of the complement-binding domain of Staphylococcus aureus protein Sbi in complex with ligand C3d. Molecular Immunology, 48(4), 452-462. https://doi.org/10.1016/j.molimm.2010.09.017