...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Infection and immunity >Processing of Pseudomonas aeruginosa Exotoxin A Is Dispensable for Cell Intoxication
【24h】

Processing of Pseudomonas aeruginosa Exotoxin A Is Dispensable for Cell Intoxication

机译：铜绿假单胞菌外毒素A的加工对于细胞中毒是必不可少的

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Exotoxin A is a major virulence factor of Pseudomonas aeruginosa. This toxin binds to a specific receptor on animal cells, allowing endocytosis of the toxin. Once in endosomes, the exotoxin can be processed by furin to generate a C-terminal toxin fragment that lacks the receptor binding domain and is retrogradely transported to the endoplasmic reticulum for retrotranslocation to the cytosol through the Sec61 channel. The toxin then blocks protein synthesis by ADP ribosylation of elongation factor 2, thereby triggering cell death. A shorter intracellular route has also been described for this toxin. It involves direct translocation of the entire toxin from endosomes to the cytosol and therefore does not rely on furin-mediated cleavage. To examine the implications of endosomal translocation in the intoxication process, we investigated whether the toxin required furin-mediated processing in order to kill cells. We used three different approaches. We first fused to the N terminus of the toxin proteins with different unfolding abilities so that they inhibited or did not inhibit endosomal translocation of the chimera. We then assayed the amount of toxin fragments delivered to the cytosol during cell intoxication. Finally we used furin inhibitors and examined the fate and intracellular localization of the toxin and its receptor. The results showed that exotoxin cytotoxicity results largely from endosomal translocation of the entire toxin. We found that the C-terminal fragment was unstable in the cytosol.
机译：外毒素A是铜绿假单胞菌（Pseudomonas aeruginosa）的主要毒力因子。该毒素与动物细胞上的特定受体结合，从而使毒素内吞。进入内体后，外毒素可以被弗林蛋白酶加工以生成缺少受体结合域的C端毒素片段，并逆行转运至内质网，通过Sec61通道逆向转运至胞质溶胶。然后，毒素通过延伸因子2的ADP核糖基化来阻止蛋白质合成，从而触发细胞死亡。还已经针对该毒素描述了较短的细胞内途径。它涉及整个毒素从内体直接转移到细胞质中，因此不依赖弗林蛋白酶介导的裂解。为了检查内吞转运在中毒过程中的意义，我们调查了毒素是否需要弗林蛋白酶介导的加工才能杀死细胞。我们使用了三种不同的方法。我们首先融合具有不同展开能力的毒素蛋白的N末端，以使其抑制或不抑制嵌合体的内体转运。然后，我们分析了细胞中毒过程中传递到细胞质的毒素片段的数量。最后，我们使用弗林蛋白酶抑制剂并检查了毒素及其受体的命运和细胞内定位。结果表明，外毒素的细胞毒性主要是由整个毒素的内体易位引起的。我们发现C端片段在细胞质中不稳定。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号