Glycan region of GPI anchored-protein is required for cytocidal oligomerization of an anticancer parasporin-2, Cry46Aa1 protein, from Bacillus thuringiensis strain A1547
Glycan region of GPI anchored-protein is required for cytocidal oligomerization of an anticancer parasporin-2, Cry46Aa1 protein, from Bacillus thuringiensis strain A1547
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DOI：
10.1016/j.jip.2016.11.008
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发表时间：
2017-01-01
影响因子：
3.4
通讯作者：
Kitada, Sakae
中科院分区：
文献类型：
--
作者：
Abe, Yuich;Inoue, Hiroshi;Kitada, Sakae
副孢子蛋白-2(Parasporin-2，PS2)，又名Cry46Aa1，是苏云金芽孢杆菌A1547菌株的抗癌蛋白，通过PS2在细胞膜上的寡聚作用引起特异性细胞损伤。虽然PS2需要糖基磷脂酰肌醇(GPI)锚定蛋白来发挥其细胞杀伤作用，但它们的确切作用尚不清楚。在这里，我们报告了GPI的多糖诱导PS2寡聚，从而导致细胞死亡。在GPI锚定蛋白缺失的中国仓鼠卵巢细胞中未观察到该毒素的细胞毒性、细胞结合和寡聚化现象。表达和酶处理分析表明，毒素的作用依赖于GPI锚定蛋白的糖核，而不是多肽部分。然而，在PS2不敏感的细胞中观察到一些GPI锚定蛋白的表面表达。这些数据表明，GPI锚定蛋白并不决定目标的特异性，而是在PS2的细胞杀伤作用中作为一种辅助受体发挥作用。(C)2016 Elsevier Inc.保留所有权利。
Parasporin-2 (PS2), alternatively named Cry46Aa1, an anticancer protein derived from Bacillus thuringiensis strain A1547, causes specific cell damage via PS2 oligomerization in the cell membrane. Although PS2 requires glycosylphosphatidylinositol (GPI)-anchored proteins for its cytocidal action, their precise role is unknown. Here, we report that the glycan of GPI induces PS2 oligomerization, which causes cell death. Cytotoxicity, cell-binding and oligomerization of the toxin were not observed in GPI-anchored protein deficient Chinese hamster ovary cells. Expression and protease-treatment analyses showed that the actions of the toxin were dependent on the glycan core, not the polypeptide moiety, of GPI-anchored proteins. However, surface expression of some GPI-anchored proteins is observed in PS2-insensitive cells. These data suggest that GPI-anchored proteins do not determine the target specificity, but instead function as a kind of coreceptor, in the cytocidal action of PS2. (C) 2016 Elsevier Inc. All rights reserved.