The crystal structure of staphylococcal enterotoxin type D reveals Zn2+-mediated homodimerization.
Bacterial superantigens, including the staphylococcal enterotoxins, are the most potent activators of T cells known and have been suggested as a causative factor in Gram-positive shock in humans. Staphylococcal enterotoxin D (SED) is dependent upon Zn2+ for high affinity interactions with MHC class II molecules and thus SED was co-crystallized with Zn2+. The crystal structure of SED has been determined in two different space groups, at 2.3 and 3.0 A resolution respectively. The three-dimensional structure of SED is similar to structures of other bacterial superantigens, although this study has revealed that SED has the unique capability of forming dimers in the presence of Zn2+. The high affinity Zn2+ site used in dimer formation is located on the surface of the beta-sheet in the C-terminal domain. Two bound metal ions are coordinated by residues from both molecules in the dimer interface and thus contribute directly to formation of the dimer. A second Zn2+ site is located on the surface close to the domain interface of the molecule. The unique feature of SED in forming a Zn2+-dependent homodimer seems to facilitate novel and biologically relevant multimeric interactions with MHC class II molecules, as shown by the induction of cytokine mRNA in human monocytes when exposed to SED and SED mutants.
Sundström
M
M
Department of Structural Biochemistry, Pharmacia and Upjohn, Stockholm, Sweden.
Abrahmsén
L
L
Antonsson
P
P
Mehindate
K
K
Mourad
W
W
Dohlsten
M
M
D001665:Binding Sites; D001704:Biopolymers; D018360:Crystallography, X-Ray; D004768:Enterotoxins / Q000737:chemistry* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D018089:Superantigens / Q000737:chemistry / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015032:Zinc / Q000737:chemistry* / Q000378:metabolism
D001704:Biopolymers; D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D011994:Recombinant Proteins; D018089:Superantigens; C019368:enterotoxin D, Staphylococcal; D015032:Zinc