Junior Research Group, Paul-Ehrlich Institute, Langen, Germany.
EMBO Rep. 2010 Oct;11(10):798-804. doi: 10.1038/embor.2010.114. Epub 2010 Sep 3.
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.
哺乳动物和原核生物的高温需求 A (HtrA) 蛋白是伴侣蛋白和丝氨酸蛋白酶,在蛋白质质量控制中发挥着重要作用。在这里,我们描述了 HtrA 的一个全新功能,并将其鉴定为来自幽门螺杆菌的一种新的分泌性毒力因子,该因子可裂解细胞黏附蛋白 E-钙黏蛋白的细胞外结构域。E-钙黏蛋白的脱落破坏了上皮屏障功能,使幽门螺杆菌能够进入细胞间隙。然后,我们设计了一种小分子抑制剂,可有效阻断 HtrA 的活性、E-钙黏蛋白的切割以及幽门螺杆菌的细胞间进入。