Structural basis of superantigen action inferred from crystal structure of toxic-shock syndrome toxin-1.
Superantigens stimulate T cells bearing particular T-cell receptor V beta sequences, so they are extremely potent polyclonal T-cell mitogens. T-cell activation is preceded by binding of superantigens to class II major histocompatibility complex (MHC) molecules. To further the structural characterization of these interactions, the crystal structure of a toxin associated with toxic-shock syndrome, TSST-1, which is a microbial superantigen, has been determined at 2.5 A resolution. The N- and C-terminal domains of the structure both contain regions involved in MHC class II association; the C-terminal domain is also implicated in binding the T-cell receptor. Despite low sequence conservation, the TSST-1 topology is similar to the structure reported for the superantigen staphylococcal enterotoxin B4. But TSST-1 lacks several of the structural features highlighted as central to superantigen activity in the staphylococcal enterotoxin B and we therefore reappraise the structural basis of superantigen action.
Acharya
K R
KR
School of Biology and Biochemistry, University of Bath, UK.
Passalacqua
E F
EF
Jones
E Y
EY
Harlos
K
K
Stuart
D I
DI
Brehm
R D
RD
Tranter
H S
HS
D000595:Amino Acid Sequence; D001427:Bacterial Toxins; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D004768:Enterotoxins / Q000737:chemistry* / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013211:Staphylococcus aureus; D013329:Structure-Activity Relationship; D018089:Superantigens / Q000737:chemistry* / Q000276:immunology
D001427:Bacterial Toxins; D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; C031818:enterotoxin B, staphylococcal