Zinc-mediated Dimerization and Its Effect on Activity and
Conformation of Staphylococcal Enterotoxin Type C*
Young-In
Chi
§,
Ingrid
Sadler¶,
Lynn M.
Jablonski¶
,
Scott D.
Callantine¶,
Claudia F.
Deobald¶,
Cynthia V.
Stauffacher, and
Gregory A.
Bohach¶
From the Department of Biological Sciences, Purdue
University, West Lafayette, Indiana 47907 and the ¶ Department of
Microbiology, Molecular Biology and Biochemistry, University of Idaho,
Moscow, Idaho 83843
Staphylococcal enterotoxins are
superantigen exotoxins that mediate food poisoning and toxic shock
syndrome in humans. Despite their structural and functional
similarities, superantigens display subtle differences in biological
properties and modes of receptor binding as a result of zinc atoms
bound differently in their crystal structures. For example, the crystal
structures of the staphylococcal enterotoxins in the type C serogroup
(SECs) contain a zinc atom coordinated by one aspartate and two
histidine residues from one molecule and another aspartate residue from
the next molecule, thus forming a dimer. This type of zinc ligation and
zinc-mediated dimerization occurs in several SECs, but not in most
other staphylococcal enterotoxin serogroups. This prompted us to
investigate the potential importance of zinc in SEC-mediated
pathogenesis. Site-directed mutagenesis was used to replace SEC zinc
binding ligands with alanine. SEC mutants unable to bind zinc did not
have major conformational alterations although they failed to form
dimers. Zinc binding was not essential for T cell stimulation,
emesis, or lethality although in general the mutants were less
pyrogenic. Thus the zinc atom in SECs might represent a non-functional
heavy atom in an exotoxin group that has diverged from related
bacterial toxins containing crucial zinc atoms.
*
This work was funded by National Research Initiative
Competitive Grants Program United States Department of Agriculture
Grant 9402399, Public Health Service Grants AI28401 and RR00166, the United Dairymen of Idaho, and a grant from the Lucille P. Markey Foundation, given to the Structural Biology Group in the
Department of Biological Sciences.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
The atomic coordinates and the structure factors (code 1ck1) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).
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