Department of Bacterial Genetics, Institute of Microbiology, Faculty of Biology, University of Warsaw, Warsaw, Poland.
Mass Spectrometry Laboratory, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.
Int J Med Microbiol. 2018 Dec;308(8):977-985. doi: 10.1016/j.ijmm.2018.08.002. Epub 2018 Aug 7.
Thioloxidoreductase HP0231 of Helicobacter pylori plays essential roles in gastric colonization and related gastric pathology. Comparative proteomics and analysis of complexes between HP0231 and its protein substrates suggested that several Hop proteins are its targets. HP0231 is a dimeric oxidoreductase that functions in an oxidizing Dsb (disulfide bonds) pathway of H. pylori. H. pylori HopQ possesses six cysteine residues, which generate three consecutive disulfide bridges. Comparison of the redox state of HopQ in wild-type cells to that in hp0231-mutated cells clearly indicated that HopQ is a substrate of HP0231. HopQ binds CEACAM1, 3, 5 and 6 (carcinoembryonic antigen-related cell adhesion molecules). This interaction enables T4SS-mediated translocation of CagA into host cells and induces host signaling. Site directed mutagenesis of HopQ (changing cysteine residues into serine) and analysis of the functioning of HopQ variants showed that HP0231 influences the delivery of CagA into host cells, in part through its impact on HopQ redox state. Introduction of a C382S mutation into HopQ significantly affects its reaction with CEACAM receptors, which disturbs T4SS functioning and CagA delivery. An additional effect of HP0231 on other adhesins and their redox state, resulting in their functional impairment, cannot be excluded.
幽门螺杆菌的硫氧还蛋白氧化还原酶 HP0231 在胃定植和相关胃病理中发挥重要作用。比较蛋白质组学和 HP0231 与其蛋白底物之间复合物的分析表明，几种 Hop 蛋白是其靶标。HP0231 是一种二聚体氧化还原酶，在幽门螺杆菌的氧化 Dsb（二硫键）途径中发挥作用。幽门螺杆菌 HopQ 含有六个半胱氨酸残基，可生成三个连续的二硫键。野生型细胞中 HopQ 的氧化还原状态与 hp0231 突变细胞中的 HopQ 的氧化还原状态进行比较，清楚地表明 HopQ 是 HP0231 的底物。HopQ 结合 CEACAM1、3、5 和 6（癌胚抗原相关细胞粘附分子）。这种相互作用使 T4SS 将 CagA 易位到宿主细胞中，并诱导宿主信号转导。HopQ 的定点突变（将半胱氨酸残基突变为丝氨酸）和对 HopQ 变体功能的分析表明，HP0231 影响 CagA 进入宿主细胞的传递，部分是通过其对 HopQ 氧化还原状态的影响。将 C382S 突变引入 HopQ 会显著影响其与 CEACAM 受体的反应，从而干扰 T4SS 的功能和 CagA 的传递。HP0231 对其他粘附素及其氧化还原状态的额外影响，导致它们的功能受损，这一点不能排除。
