Identification of a secondary zinc-binding site in staphylococcal enterotoxin C2. Implications for superantigen recognition.
The previously determined crystal structure of the superantigen staphylococcal enterotoxin C2 (SEC2) showed binding of a single zinc ion located between the N- and C-terminal domains. Here we present the crystal structure of SEC2 determined to 2.0 A resolution in the presence of additional zinc. The structure revealed the presence of a secondary zinc-binding site close to the major histocompatibility complex (MHC)-binding site of the toxin and some 28 A away from the primary zinc-binding site of the toxin found in previous studies. T cell stimulation assays showed that varying the concentration of zinc ions present affected the activity of the toxin and we observed that high zinc concentrations considerably inhibited T cell responses. This indicates that SEC2 may have multiple modes of interaction with the immune system that are dependent on serum zinc levels. The potential role of the secondary zinc-binding site and that of the primary one in the formation of the TCR.SEC2.MHC complex are considered, and the possibility that zinc may regulate the activity of SEC2 as a toxin facilitating different T cell responses is discussed.
Papageorgiou
Anastassios C
AC
Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK.
Baker
Matthew D
MD
McLeod
Julie D
JD
Goda
Sayed K
SK
Manzotti
Claire N
CN
Sansom
David M
DM
Tranter
Howard S
HS
Acharya
K Ravi
KR
D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry; D001665:Binding Sites; D016466:CHO Cells; D002455:Cell Division; D006224:Cricetinae; D018360:Crystallography, X-Ray; D019281:Dimerization; D004768:Enterotoxins / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D013601:T-Lymphocytes / Q000378:metabolism; D014162:Transfection; D014961:X-Ray Diffraction; D015032:Zinc / Q000737:chemistry*
D000942:Antigens, Bacterial; D004768:Enterotoxins; C034959:enterotoxin C, staphylococcal; D015032:Zinc