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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Structural basis of toxicity and immunity in contact-dependent growth inhibition (CDI) systems
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Structural basis of toxicity and immunity in contact-dependent growth inhibition (CDI) systems

机译:接触依赖性生长抑制(CDI)系统中毒性和免疫力的结构基础

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摘要

Contact-dependent growth inhibition (CDI) systems encode polymorphic toxin/immunity proteins that mediate competition between neighboring bacterial cells. We present crystal structures of CDI toxin/ immunity complexes from Escherichia coli EC869 and Burkholderia pseudomallei 1026b. Despite sharing little sequence identity, the toxin domains are structurally similar and have homology to endo-nucleases. The EC869 toxin is a Zn~(2+)-dependent DNase capable of completely degrading the genomes of target cells, whereas the Bp1026b toxin cleaves the aminoacyl acceptor stems of tRNA molecules. Each immunity protein binds and inactivates its cognate toxin in a unique manner. The EC869 toxin/immunity complex is stabilized through an unusual β-augmentation interaction. In contrast, the Bp1026b immunity protein exploits shape and charge complementarity to occlude the toxin active site. These structures represent the initial glimpse into the CDI toxin/immunity network, illustrating how sequence-diverse toxins adopt convergent folds yet retain distinct binding interactions with cognate immunity proteins. Moreover, we present visual demonstration of CDI toxin delivery into a target cell.
机译:接触依赖性生长抑制(CDI)系统编码介导相邻细菌细胞之间竞争的多态毒素/免疫蛋白。我们目前从大肠杆菌EC869和假伯克霍尔德氏菌1026b CDI毒素/免疫复合物的晶体结构。尽管几乎没有序列同一性,但是毒素结构域在结构上相似并且与核酸内切酶具有同源性。 EC869毒素是一种能够完全降解靶细胞基因组的依赖Zn〜(2+)的DNase,而Bp1026b毒素可裂解tRNA分子的氨酰基受体茎。每个免疫蛋白都以独特的方式结合并使其同源毒素失活。 EC869毒素/免疫复合物通过异常的β增强相互作用而稳定。相反,Bp1026b免疫蛋白利用形状和电荷互补性来遮盖毒素活性位点。这些结构代表了对CDI毒素/免疫网络的初步了解,说明了序列多样的毒素如何采用会聚的折叠,但仍保留与同源免疫蛋白的独特结合相互作用。此外,我们提出CDI毒素传递到目标细胞的视觉演示。

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  • 作者单位

    Departments of Molecular Biology and Biochemistry University of California, Irvine, CA 92697;

    Department of Chemistry and Biochemistry University of California, Santa Barbara, CA 93106;

    Department of Molecular, Cellular, and Developmental Biology University of California, Santa Barbara, CA 93106;

    Departments of Molecular Biology and Biochemistry University of California, Irvine, CA 92697;

    Department of Molecular, Cellular, and Developmental Biology University of California, Santa Barbara, CA 93106,Biomolecular Science and Engineering Program, University of California, Santa Barbara, CA 93106;

    Department of Molecular, Cellular, and Developmental Biology University of California, Santa Barbara, CA 93106,Biomolecular Science and Engineering Program, University of California, Santa Barbara, CA 93106;

    Departments of Molecular Biology and Biochemistry University of California, Irvine, CA 92697,Pharmaceutical Sciences, University of California, Irvine, CA 92697;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    structural biology; bacterial competition; β-complementation; tRNase activity;

    机译:结构生物学;细菌竞争;β-补体;tRNase活性;

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