Sundström M, Abrahmsén L, Antonsson P, Mehindate K, Mourad W, Dohlsten M
Department of Structural Biochemistry, Pharmacia and Upjohn, Stockholm, Sweden.
EMBO J. 1996 Dec 16;15(24):6832-40.
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.
包括葡萄球菌肠毒素在内的细菌超抗原是已知的最有效的T细胞激活剂，并被认为是人类革兰氏阳性菌休克的一个致病因素。葡萄球菌肠毒素D（SED）与MHC II类分子的高亲和力相互作用依赖于Zn2+，因此SED与Zn2+一起进行了共结晶。已分别在两种不同的空间群中以2.3 Å和3.0 Å的分辨率确定了SED的晶体结构。SED的三维结构与其他细菌超抗原的结构相似，不过这项研究表明SED在Zn2+存在的情况下具有形成二聚体的独特能力。用于二聚体形成的高亲和力Zn2+位点位于C端结构域β折叠的表面。两个结合的金属离子由二聚体界面中两个分子的残基配位，因此直接促成了二聚体的形成。第二个Zn2+位点位于靠近分子结构域界面的表面。SED形成依赖于Zn2+的同源二聚体这一独特特征似乎有助于与MHC II类分子进行新的且具有生物学相关性的多聚体相互作用，如人类单核细胞在暴露于SED和SED突变体时细胞因子mRNA的诱导所显示的那样。
