Both the p33 and p55 Subunits of the Helicobacter pylori VacA Toxin Are Targeted to Mammalian Mitochondria
Both the p33 and p55 Subunits of the Helicobacter pylori VacA Toxin Are Targeted to Mammalian Mitochondria
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DOI：
10.1016/j.jmb.2010.06.065
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发表时间：
2010-09-03
影响因子：
5.6
通讯作者：
Gabriel, Kipros
中科院分区：
文献类型：
--
作者：
Foo, Jung Hock;Culvenor, Janetta G.;Gabriel, Kipros
幽门螺杆菌感染会导致消化性溃疡和胃癌。H. pylori是二分空泡细胞毒素A，VacA。该毒素被认为作为两个亚基进入宿主细胞：p55亚基（55 kDa）和p33亚基（33 kDa）。在生物化学水平上，已经表明VacA是通过在生物膜中组装由p33亚基和p55亚基组成的大的多聚体孔形成的。VacA的主要靶细胞器之一是线粒体。由于只有p33亚基被报道转移到线粒体中，而p55亚基没有被输入，因此关于VacA是否组装到线粒体膜的孔中一直存在争议。在这里，我们显示p55蛋白与p33蛋白亚基一起沿着进入线粒体。p33亚基与线粒体内膜完整结合，并且p33亚基和p55亚基都暴露于线粒体膜间隙。它们的共定位表明它们可以重新组装并在线粒体内膜中形成孔。(C)2010爱思唯尔有限公司保留所有权利。
Helicobacter pylori infection causes peptic ulcers and gastric cancer. A major toxin secreted by H. pylori is the bipartite vacuolating cytotoxin A, VacA. The toxin is believed to enter host cells as two subunits: the p55 subunit (55 kDa) and the p33 subunit (33 kDa). At the biochemical level, it has been shown that VacA forms through the assembly of large multimeric pores composed of both the p33 subunit and the p55 subunit in biological membranes. One of the major target organelles of VacA is the mitochondria. Since only the p33 subunit has been reported to be translocated into mitochondria and the p55 subunit is not imported, it has been contentious as to whether VacA assembles into pores in a mitochondrial membrane. Here we show the p55 protein is imported into the mitochondria along with the p33 protein subunit. The p33 subunit integrally associates with the mitochondrial inner membrane, and both the p33 subunit and the p55 subunit are exposed to the mitochondrial intermembrane space. Their colocalization suggests that they could reassemble and form a pore in the inner mitochondrial membrane. (C) 2010 Elsevier Ltd. All rights reserved.