Structures of five mutants of toxic shock syndrome toxin-1 with reduced biological activity

Cathleen A. Earhart, David T. Mitchell, Debra L. Murray, Denise M. Pinheiro, Masazumi Matsumura, Patrick M. Schlievert, Douglas H. Ohlendorf

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26 Scopus citations

Abstract

The three-dimensional structures of five mutants of toxic shock syndrome toxin-1 (TSST-1) have been determined. These mutations are in the long central α helix and are useful in mapping portions of TSST-1 involved in superantigenicity and lethality. The T128A, H135A, Q139K, and I140T mutations appear to reduce superantigenicity by altering the properties of the T-cell receptor interaction surface. The Q136A mutation is at a largely buried site and causes a dramatic change in the conformation of the β7-β9 loop which covers the back of the central α helix. As this mutation has the unique ability to reduce the toxin's lethality in rabbits while retaining its superantigenicity, it raises the possibility that this rear loop mediates the ability of TSST-1 to induce lethality and suggests a route for producing nonlethal toxins for therapeutic development.

Original languageEnglish (US)
Pages (from-to)7194-7202
Number of pages9
JournalBiochemistry
Volume37
Issue number20
DOIs
StatePublished - May 19 1998

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    Earhart, C. A., Mitchell, D. T., Murray, D. L., Pinheiro, D. M., Matsumura, M., Schlievert, P. M., & Ohlendorf, D. H. (1998). Structures of five mutants of toxic shock syndrome toxin-1 with reduced biological activity. Biochemistry, 37(20), 7194-7202. https://doi.org/10.1021/bi9721896