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Structures of Five Mutants of Toxic Shock Syndrome Toxin-1 with Reduced Biological Activity ,

1998; American Chemical Society; Volume: 37; Issue: 20 Linguagem: Inglês

10.1021/bi9721896

1943-295X

C.A. Earhart, David Mitchell, Debra L. Murray, Denise M. Pinheiro, Masazumi Matsumura, Patrick M. Schlievert, D.H. Ohlendorf,

Cardiac electrophysiology and arrhythmias

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.