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首页> 外文期刊>Infection and immunity >The Coupling Protein Cagβ and Its Interaction Partner CagZ Are Required for Type IV Secretion of the Helicobacter pylori CagA Protein
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The Coupling Protein Cagβ and Its Interaction Partner CagZ Are Required for Type IV Secretion of the Helicobacter pylori CagA Protein

机译：幽门螺杆菌CagA蛋白的IV型分泌需要偶联蛋白Cagβ及其相互作用伴侣CagZ

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Bacterial type IV secretion systems are macromolecule transporters with essential functions for horizontal gene transfer and for symbiotic and pathogenic interactions with eukaryotic host cells. Helicobacter pylori, the causative agent of type B gastritis, peptic ulcers, gastric adenocarcinoma, and mucosa-associated lymphoid tissue (MALT) lymphoma, uses the Cag type IV secretion system to inject its effector protein CagA into gastric cells. This protein translocation results in altered host cell gene expression profiles and cytoskeletal rearrangements, and it has been linked to cancer development. Interactions of CagA with host cell proteins have been studied in great detail, but little is known about the molecular details of CagA recognition as a type IV secretion substrate or of the translocation process. Apart from components of the secretion apparatus, we previously identified several CagA translocation factors that are either required for or support CagA translocation. To identify protein-protein interactions between these translocation factors, we used a yeast two-hybrid approach comprising all cag pathogenicity island genes. Among several other interactions involving translocation factors, we found a strong interaction between the coupling protein homologue Cagβ (HP0524) and the Cag-specific translocation factor CagZ (HP0526). We show that CagZ has a stabilizing effect on Cagβ, and we demonstrate protein-protein interactions between the cytoplasmic part of Cagβ and CagA and between CagZ and Cagβ, using immunoprecipitation and pull-down assays. Together, our data suggest that these interactions represent a substrate-translocation factor complex at the bacterial cytoplasmic membrane.
机译：细菌IV型分泌系统是大分子转运蛋白，具有水平基因转移以及与真核宿主细胞共生和致病性相互作用的基本功能。幽门螺杆菌是B型胃炎，消化性溃疡，胃腺癌和黏膜相关淋巴样组织（MALT）淋巴瘤的病原体，它使用Cag IV型分泌系统将其效应蛋白CagA注入胃中细胞。这种蛋白质易位导致宿主细胞基因表达谱和细胞骨架重排的改变，并且它与癌症的发展有关。已经对CagA与宿主细胞蛋白的相互作用进行了详细的研究，但对CagA识别为IV型分泌底物或转运过程的分子细节知之甚少。除了分泌设备的组成部分，我们之前还确定了CagA易位所需或支持的几种CagA易位因子。为了鉴定这些易位因子之间的蛋白质-蛋白质相互作用，我们使用了包含所有 cag 致病性岛基因的酵母双杂交方法。在涉及易位因子的其他几种相互作用中，我们发现偶联蛋白同源物Cagβ（HP0524）与Cag特异性易位因子CagZ（HP0526）之间存在强相互作用。我们显示，CagZ对Cagβ具有稳定作用，并且我们使用免疫沉淀和下拉测定法证明了Cagβ和CagA的细胞质部分之间以及CagZ和Cagβ之间的蛋白质-蛋白质相互作用。总之，我们的数据表明这些相互作用代表了细菌细胞质膜上的底物易位因子复合物。

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