Crystal structure of the superantigen enterotoxin C2 from Staphylococcus aureus reveals a zinc-binding site

Structure. 1995 Aug 15;3(8):769-79. doi: 10.1016/s0969-2126(01)00212-x.


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 A 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.

Conclusions: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Toxins*
  • Binding Sites
  • Crystallography, X-Ray / methods
  • Enterotoxins / chemistry*
  • Enterotoxins / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Secondary*
  • Sequence Homology, Amino Acid
  • Staphylococcus aureus* / immunology
  • Superantigens / chemistry*
  • Superantigens / metabolism
  • Zinc / metabolism*


  • Bacterial Toxins
  • Enterotoxins
  • Superantigens
  • enterotoxin F, Staphylococcal
  • enterotoxin B, staphylococcal
  • enterotoxin C, staphylococcal
  • Zinc