Menestrina G, Belmonte G, Parisi V, Morante S
Dipartimento di Fisica, Università di Trento, Italy.
FEMS Microbiol Immunol. 1992 Sep;5(1-3):19-28. doi: 10.1111/j.1574-6968.1992.tb05882.x.
Staphylococcus aureus alpha-toxin makes cells and model membranes permeable to ions and uncharged molecules by opening oligomeric pores of uniform size. Its primary sequence reveals peculiar features which give some hints on the structure of the pore. A flexible region separating the toxin into two halves, several amphiphilic beta-strands and two amphiphilic alpha-helices long enough to span the hydrophobic core of the lipid bilayer are predicted. In analogy to bacterial porins, we propose that the inner walls of the pore are, at least in part, built by an amphiphilic beta-barrel. The model is consistent with circular dichroism data and with the electrophysiological properties of the pore. Functional information on this toxin were obtained by chemical modification of its four histidine residues. Specific carbethoxylation suggested they have different roles: one is required for specific receptor binding, one for oligomerisation and two for unspecific lipid binding. A tentative assignment of each histidine to its specific role is done on the basis of the structural predictions. A functionally related hemolysin, Aeromonas hydrophyla aerolysin, reveals remarkably similar features including the presence and location of histidines involved in receptor binding and oligomerisation.
金黄色葡萄球菌α毒素通过打开大小均匀的寡聚孔，使细胞和模型膜对离子和不带电荷的分子具有通透性。其一级序列显示出一些独特特征，为孔的结构提供了一些线索。预测有一个柔性区域将毒素分为两半，还有几条两亲性β链和两条足够长以跨越脂质双层疏水核心的两亲性α螺旋。与细菌孔蛋白类似，我们提出孔的内壁至少部分由两亲性β桶构成。该模型与圆二色性数据以及孔的电生理特性一致。通过对其四个组氨酸残基进行化学修饰，获得了关于这种毒素的功能信息。特异性乙氧羰基化表明它们具有不同的作用：一个用于特异性受体结合，一个用于寡聚化，两个用于非特异性脂质结合。根据结构预测对每个组氨酸的特定作用进行了初步分配。一种功能相关的溶血素，嗜水气单胞菌气溶素，显示出非常相似的特征，包括参与受体结合和寡聚化的组氨酸的存在和位置。
