Rossjohn J, Feil S C, McKinstry W J, Tweten R K, Parker M W
The Ian Potter Foundation Protein Crystallography Laboratory, St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
Cell. 1997 May 30;89(5):685-92. doi: 10.1016/s0092-8674(00)80251-2.
The mechanisms by which proteins gain entry into membranes is a fundamental problem in biology. Here, we present the first crystal structure of a thiol-activated cytolysin, perfringolysin O, a member of a large family of toxins that kill eukaryotic cells by punching holes in their membranes. The molecule adopts an unusually elongated shape rich in beta sheet. We have used electron microscopy data to construct a detailed model of the membrane channel form of the toxin. The structures reveal a novel mechanism for membrane insertion. Surprisingly, the toxin receptor, cholesterol, appears to play multiple roles: targeting, promotion of oligomerization, triggering a membrane insertion competent form, and stabilizing the membrane pore.
蛋白质进入细胞膜的机制是生物学中的一个基本问题。在此，我们展示了硫醇激活的细胞溶素——产气荚膜梭菌溶血素O的首个晶体结构，它是一大类毒素家族的成员，这类毒素通过在真核细胞膜上打孔来杀死细胞。该分子呈现出一种异常细长且富含β折叠的形状。我们利用电子显微镜数据构建了毒素膜通道形式的详细模型。这些结构揭示了一种新的膜插入机制。令人惊讶的是，毒素受体胆固醇似乎发挥着多种作用：靶向定位、促进寡聚化、触发膜插入活性形式以及稳定膜孔。
