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首页> 外文期刊>The Journal of biological chemistry >Identification of Chromosomal HP0892-HP0893 Toxin-Antitoxin Proteins in Helicobacter pylori and Structural Elucidation of Their Protein-Protein Interaction
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Identification of Chromosomal HP0892-HP0893 Toxin-Antitoxin Proteins in Helicobacter pylori and Structural Elucidation of Their Protein-Protein Interaction

机译：染色体HP0892-HP0893在幽门螺杆菌中毒素 - 抗毒素蛋白的鉴定及其蛋白质 - 蛋白质相互作用的结构阐明

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Bacterial chromosomal toxin-antitoxin (TA) systems have been proposed not only to play an important role in the stress response, but also to be associated with antibiotic resistance. Here, we identified the chromosomal HP0892-HP0893 TA proteins in the gastric pathogen, Helicobacter pylori, and structurally characterized their protein-protein interaction. Previously, HP0892 protein was suggested to be a putative TA toxin based on its structural similarity to other RelE family TA toxins. In this study, we demonstrated that HP0892 binds to HP0893 strongly with a stoichiometry of 1:1, and HP0892-HP0893 interaction occurs mainly between the N-terminal secondary structure elements of HP0892 and the C-terminal region of HP0893. HP0892 cleaved mRNA in vitro, preferentially at the 5′ end of A or G, and the RNase activity of HP0892 was inhibited by HP0893. In addition, heterologous expression of HP0892 in Escherichia coli cells led to cell growth arrest, and the cell toxicity of HP0892 was neutralized by co-expression with HP0893. From these results and a structural comparison with other TA toxins, it is concluded that HP0892 is a toxin with intrinsic RNase activity and HP0893 is an antitoxin against HP0892 from a TA system of H. pylori. It has been known that hp0893 gene and another TA antitoxin gene, hp0895, of H. pylori, are both genomic open reading frames that correspond to genes that are potentially expressed in response to interactions with the human gastric mucosa. Therefore, it is highly probable that TA systems of H. pylori are involved in virulence of H. pylori.
机译：已经提出了细菌染色体毒素 - 抗毒素（TA）系统不仅在应力反应中发挥着重要作用，而且与抗生素抗性相关。在这里，我们鉴定了胃病原体，幽门螺杆菌的染色体HP0892-HP0893 TA蛋白，并在结构表征其蛋白质 - 蛋白质相互作用。以前，提出HP0892蛋白是基于其与其他Rele家族Ta毒素的结构相似性的推定的Ta毒素。在该研究中，我们证明HP0892强烈地与1：1的化学计量强烈结合HP0893，HP0892-HP0893相互作用主要发生在HP0892的N-末端二次结构元素和HP0893的C末端区域之间。 HP0892在体外切割mRNA，优先于A或G的5'末端，HP0893抑制HP0892的RNase活性。此外，HP0892在大肠杆菌细胞中的异源表达导致细胞生长停滞，HP0892的细胞毒性通过与HP0893的共同表达中和。从这些结果和与其他Ta毒素的结构比较，得出结论，HP0892是具有内在RNase活性的毒素，HP0893是来自H.幽门螺杆菌的TA系统的抗毒素对抗HP0892。已知HP0893基因及其另一个TA抗毒素基因HP0895的H.Pylori是对应于响应于与人胃粘膜的相互作用可能表达的基因的基因组开放阅读框。因此，非常可能的是，H.Pylori的Ta系统参与了幽门螺杆菌的毒力。

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