Helicobacter pylori HtrA is a new secreted virulence factor that cleaves E-cadherin to disrupt intercellular adhesion
Helicobacter pylori HtrA is a new secreted virulence factor that cleaves E-cadherin to disrupt intercellular adhesion
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DOI：
10.1038/embor.2010.114
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发表时间：
2010-10-01
期刊：
影响因子：
7.7
通讯作者：
Wessler, Silja
中科院分区：
文献类型：
--
作者：
Hoy, Benjamin;Loewer, Martin;Wessler, Silja
哺乳动物和原核生物的高温需要A（HtrA）蛋白是分子伴侣和丝氨酸蛋白酶，在蛋白质质量控制中具有重要作用。在这里，我们描述了一个全新的功能HtrA，并确定它作为一个新的分泌的毒力因子幽门螺杆菌，切割细胞粘附蛋白E-钙粘蛋白的胞外域。E-钙粘蛋白脱落破坏上皮屏障功能，使H。pylori设计来进入细胞间隙。然后，我们设计了一种小分子抑制剂，有效地阻断HtrA活性，E-钙粘蛋白切割和H.幽门螺杆菌。
Mammalian and prokaryotic high-temperature requirement A (HtrA) proteins are chaperones and serine proteases with important roles in protein quality control. Here, we describe an entirely new function of HtrA and identify it as a new secreted virulence factor from Helicobacter pylori, which cleaves the ectodomain of the cell-adhesion protein E-cadherin. E-cadherin shedding disrupts epithelial barrier functions allowing H. pylori designed to access the intercellular space. We then designed a small-molecule inhibitor that efficiently blocks HtrA activity, E-cadherin cleavage and intercellular entry of H. pylori.