CRYSTAL-STRUCTURE OF THE SUPERANTIGEN ENTEROTOXIN C2 FROM STAPHYLOCOCCUS-AUREUS REVEALS A ZINC-BINDING SITE

Background: Staphylococcus aureus enterotoxin C2 (SEC2) belongs to a family' of proteins, termed 'superantigens', that form complexes with class II MHC molecules enabling them to activate a substantial number of T cells. Although superantigens seem to act by a common mechanism, they vary in many of their specific interactions and biological properties. Comparison of the structure of SEC2 with those of two other superantigens - staphylococcal enterotoxin B (SEE) and toxic shock syndrome toxin-1 (TSST-1) - may provide insight into their mode of action. Results: The crystal structure of SEC2 has been determined at 2.0 Angstrom resolution. The overall topology of the molecule resembles that of SEE and TSST-1, and the regions corresponding to the MHC class II and T-cell receptor binding sites on SEE are quite similar in SEC2. A unique feature of SEC2 is the presence of a zinc ion located in a solvent-exposed region at the interface between the two domains of the molecule. The zinc ion is coordinated to Asp83, His118, His122 and Asp9* (from the neighbouring molecule in the crystal lattice). Atomic absorption spectrometry demonstrates that zinc is also bound to SEC2 in solution. Conclusions: SEC2 appears to be capable of binding to MHC class II molecules in much the same manner as SEE. However, structure-function studies have suggested an alternative binding mode that involves a different site on the toxin. The zinc ion of SEC2 lies within this region and thus may be important for complex formation, for example by acting as a bridge between the two molecules. Other possible roles for the metal cation, including a catalytic one, are also considered.