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

Anastassios C. Papageorgiou, K. Ravi Acharya, Robert Shapiro, Edward F. Passalacqua, Rossalyn D. Brehm, Howard S. Tranter

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)769-779
Number of pages11
JournalStructure
Volume3
Issue number8
DOIs
Publication statusPublished - 1 Jan 1995

Keywords

  • enterotoxin
  • Staphylococcus aureus
  • superantigen
  • X-ray crystallography
  • zinc binding

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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