Crystal structure of a biologically inactive mutant of toxic shock syndrome toxin-1 at 2.5 Å resolution

Anastassios C. Papageorgiou, Conrad P. Quinn, David Beer, Rossalyn D. Brehm, Howard S. Tranter, Peter F. Bonventre, K. Ravi Acharya

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Abstract

Toxic shock syndrome toxin-1 (TSST-1) is one of a family of staphylococcal exotoxins recognized as microbial superantigens. The toxin plays a dominant role in the genesis of toxic shock in humans through a massive activation of the immune system. This potentially lethal illness occurs as a result of the interaction of TSST-1 with a significant proportion of the T-cell repertoire. TSST-1, like other superantigens, can bind directly to class II major histocompatibility (MHC class II) molecules prior to its interaction with entire families of Vβ chains of the T-cell receptor (TCR). The three-dimensional structure of a mutant (His-135-Ala) TSST-1 was compared with the structure of the native (wild-type) TSST-1 at 2.5 Å resolution. The replacement of His 135 of TSST-1 with an Ala residue results in the loss of T-cell mitogenicity and toxicity in experimental animals. This residue, postulated to be directly involved in the toxin-TCR interactions, is located on the major helix α2, which forms the backbone of the molecule and is exposed to the solvent. In the molecular structure of the mutant toxin, the helix α2 remains unaltered, but the His to Ala modification causes perturbations on the neighboring helix α1 by disrupting helix-helix interactions. Thus, the effects on TCR binding of the His 135 residue could actually be mediated, wholly or in part, by the α1 helix.

Original languageEnglish
Pages (from-to)1737-1741
Number of pages5
JournalProtein Science
Volume5
Issue number8
DOIs
Publication statusPublished - 1 Jan 1996

Keywords

  • Staphylococcus aureus
  • superantigen
  • T-cell receptor
  • toxic shock syndrome toxin-1
  • X-ray crystallography

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Papageorgiou, A. C., Quinn, C. P., Beer, D., Brehm, R. D., Tranter, H. S., Bonventre, P. F., & Acharya, K. R. (1996). Crystal structure of a biologically inactive mutant of toxic shock syndrome toxin-1 at 2.5 Å resolution. Protein Science, 5(8), 1737-1741. https://doi.org/10.1002/pro.5560050826