Molecular topography of toxic shock syndrome toxin 1 as revealed by spectroscopic studies.

Molecular characterization of toxic shock syndrome toxin 1 has been carried out and compared with a group of functionally related staphylococcal enterotoxins. The secondary structure analysis of the far-UV circular dichroic spectrum of toxic shock syndrome toxin 1 revealed 6.25% alpha-helix, 51.25% beta-pleated sheets, 9.0% beta-turns, and 33.5% random coils. The pattern, in general, was similar to the staphylococcal enterotoxins. Four antigenic sites have been predicted for toxic shock syndrome toxin 1 by using the secondary structure information in combination with the hydrophilicity calculation. The location of the antigenic sites, in general, agrees with the experimental results. Topographical analysis of the tyrosine residues as determined by second-derivative UV spectroscopy [Ragone, R., Colonna, G., Balestrieri, C., Servillo, L., & Irace, G. (1984) Biochemistry 23, 1871-1875] showed that six of nine tyrosine residues are exposed to aqueous solvent. Tryptophan fluorescence quenching studies with an anionic surface quencher, I-, and a neutral quencher, acrylamide, revealed that almost all of the tryptophan residues are buried in the protein matrix as their accessibility to the surface quencher is very low (17%). Since there are only three tryptophan residues in the amino acid sequence of the toxic shock syndrome toxin 1 and there is a tyrosine residue (Tyr-15, Tyr-115, and Tyr-153) next to each of the tryptophan residues (Trp-14, Trp-116, and Trp-154), it appears the tyrosine residues not exposed to the aqueous solvent are those next to the tryptophan residues. Functional implications of the topography of the tryptophan and tyrosine residues are assessed.