Crystal structure of the streptococcal superantigen SPE-C: dimerization and zinc binding suggest a novel mode of interaction with MHC class II molecules.
Bacterial superantigens are small proteins that have a very potent stimulatory effect on T lymphocytes through their ability to bind to both MHC class II molecules and T-cell receptors. We have determined the three-dimensional structure of a Streptococcal superantigen, SPE-C, at 2.4 A resolution. The structure shows that SPE-C has the usual superantigen fold, but that the surface that forms a generic, low-affinity MHC-binding site in other superantigens is here used to create a SPE-C dimer. Instead, MHC class II binding occurs through a zinc binding site that is analogous to a similar site in staphylococcal enterotoxin A. Consideration of the SPE-C dimer suggests a novel mechanism for promotion of MHC aggregation and T-cell activation.
Roussel
A
A
Department of Biochemistry, Massey University, Palmerston North, New Zealand.
Anderson
B F
BF
Baker
H M
HM
Fraser
J D
JD
Baker
E N
EN
D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D019281:Dimerization; D004768:Enterotoxins / Q000276:immunology; D005098:Exotoxins / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D008213:Lymphocyte Activation; D008565:Membrane Proteins; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D013297:Streptococcus pyogenes / Q000276:immunology*; D018089:Superantigens / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D015032:Zinc / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; D005098:Exotoxins; D000949:Histocompatibility Antigens Class II; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; C117980:SpeA protein, Streptococcus pyogenes; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; C027951:erythrogenic toxin; D015032:Zinc