Abrami L, Fivaz M, van der Goot F G
Département de Biochimie, Université de Genève, Switzerland.
Int J Med Microbiol. 2000 Oct;290(4-5):363-7. doi: 10.1016/S1438-4221(00)80042-9.
Aerolysin secreted by the human pathogen Aeromonas hydrophila belongs to a group of bacterial toxins that are hemolytic and form channels in biological membranes. The toxin is secreted as an inactive precursor proaerolysin that must be proteolytically processed at its C-terminus to become active. The toxin then polymerizes into a heptameric ring that is amphipathic and can insert into a lipid bilayer and form a pore. We have examined these various steps at the surface of target cells. The toxin binds to specific receptors. Various receptors have been identified, all of which are anchored to the plasma membrane via a glycosylphosphatidyl inositol (GPI)-anchored moiety. The GPI anchor confers to the protein that is linked to it two usual properties: (i) the protein has a higher lateral mobility in a phospholipid bilayer than its transmembrane counterpart, (ii) the protein has the capacity to transiently associate with cholesterol-glycosphingolipid-rich microdomains. We have shown that both these properties of GPI-anchored proteins are exploited by proaerolysin bound to its receptor. The high lateral mobility within the phosphoglyceride region of the plasma membrane favors the encounter of the protoxin with its converting enzyme furin. The ability to associate with microdomains on the other hand favors the oligomerization process presumably by concentrating the toxin locally.
由人类病原体嗜水气单胞菌分泌的气溶素属于一类细菌毒素，这类毒素具有溶血作用，并能在生物膜上形成通道。该毒素以无活性的前体气溶素原形式分泌，必须在其C末端进行蛋白水解加工才能变得有活性。然后，该毒素聚合成七聚体环，这种环具有两亲性，可插入脂质双层并形成孔道。我们已经在靶细胞表面研究了这些不同的步骤。毒素与特定受体结合。已鉴定出多种受体，所有这些受体都通过糖基磷脂酰肌醇（GPI）锚定部分锚定在质膜上。GPI锚赋予与其相连的蛋白质两个常见特性：（i）该蛋白质在磷脂双层中的横向流动性高于其跨膜对应物，（ii）该蛋白质具有与富含胆固醇 - 糖鞘脂的微结构域瞬时结合的能力。我们已经表明，与受体结合的气溶素原利用了GPI锚定蛋白的这两个特性。质膜磷酸甘油区域内的高横向流动性有利于前毒素与其转化酶弗林蛋白酶相遇。另一方面，与微结构域结合的能力可能通过局部浓缩毒素而有利于寡聚化过程。
