Abstract
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 (SEB) 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 å resolution. The overall topology of the molecule resembles that of SEB and TSST-1, and the regions corresponding to the MHC class II and T-cell receptor binding sites on SEB 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. Conclusion SEC2 appears to be capable of binding to MHC class II molecules in much the same manner as SEB. 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.
| Original language | English |
|---|---|
| Pages (from-to) | 769-779 |
| Number of pages | 11 |
| Journal | Structure |
| Volume | 3 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 1 Jan 1995 |
Funding
We thank Don Wiley and his colleagues for providing the atomic coordinates of SEB–HLA-DR1 and TSST–HLA-DR1 complexes, Bert Vallee and Peter Hambleton for support and encouragement. KRA would specially like to acknowledge Anthony Rees for encouragement to initiate the superantigen work at Bath University. We are grateful to the staff at SRS, Daresbury, Demetres Leonidas and Ashley Pike for assistance with data collection, Daniel Strydom for amino acid analysis, James Riordan, David Auld, Vasanta Subramanian and Laurie Irons for helpful discussions. This work was supported by the Medical Research Council and the Nuffield Foundation, UK through grants to KRA. We thank the Science and Engineering Research Council, UK for a CASE award to EFP. Robert Shapiro, Center for Biochemical and Biophysical Sciences and Medicine and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA. Rossalyn D Brehm and Howard S Tranter, Developmental Production Department, Production Division, Centre for Applied Microbiology and Research, Porton Down, Salisbury SP4 OJG, UK.
Keywords
- enterotoxin
- Staphylococcus aureus
- superantigen
- X-ray crystallography
- zinc binding
ASJC Scopus subject areas
- Structural Biology
- Molecular Biology