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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Lsr2 is a nucleoid-associated protein that targets AT-rich sequences and virulence genes in Mycobacterium tuberculosis
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Lsr2 is a nucleoid-associated protein that targets AT-rich sequences and virulence genes in Mycobacterium tuberculosis

机译:Lsr2是一种与核苷酸类似的蛋白,靶向结核分枝杆菌中富含AT的序列和毒力基因

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摘要

Bacterial nucleoid-associated proteins play important roles in chromosome organization and global gene regulation. We find that Lsr2 of Mycobacterium tuberculosis is a unique nucleoid-associated protein that binds AT-rich regions of the genome, including genomic islands acquired by horizontal gene transfer and regions encoding major virulence factors, such as the ESX secretion systems, the lipid virulence factors PDIM and PGL, and the PE/PPE families of antigenic proteins. Comparison of genome-wide binding data with expression data indicates that Lsr2 binding results in transcriptional repression. Domain-swapping experiments demonstrate that Lsr2 has an N-terminal dimerization domain and a C-terminal DNA-binding domain. Nuclear magnetic resonance analysis of the DNA-binding domain of Lsr2 and its interaction with DNA reveals a unique structure and a unique mechanism that enables Lsr2 to discriminately target AT-rich sequences through interactions with the minor groove of DNA. Taken together, we provide evidence that mycobacteria have employed a structurally distinct molecule with an apparently different DNA recognition mechanism to achieve a function similar to the Enterobacteriaceae H-NS, likely coordinating global gene regulation and virulence in this group of medically important bacteria.
机译:细菌核苷相关蛋白在染色体组织和全球基因调控中起重要作用。我们发现结核分枝杆菌的Lsr2是一种独特的与核苷酸结合的蛋白,可结合基因组中AT丰富的区域,包括通过水平基因转移获得的基因组岛和编码主要毒力因子(例如ESX分泌系统,脂质毒力因子)的区域PDIM和PGL,以及抗原蛋白的PE / PPE家族。全基因组结合数据与表达数据的比较表明Lsr2结合导致转录抑制。域交换实验证明Lsr2具有N端二聚化域和C端DNA结合域。 Lsr2的DNA结合域的核磁共振分析及其与DNA的相互作用揭示了独特的结构和独特的机制,使Lsr2能够通过与DNA的小沟相互作用来区别性地靶向富含AT的序列。两者合计,我们提供的证据表明,分枝杆菌已采用结构上截然不同的分子,具有明显不同的DNA识别机制,以实现类似于肠杆菌科H-NS的功能,这很可能在这组医学上重要的细菌中协调了整体基因的调控和毒力。

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    Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada;

    rnBeijing NMR Center, Peking University, Beijing 100871, China School of Life Sciences, Peking University, Beijing 100871, China;

    rnDepartment of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada;

    rnDepartment of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada;

    rnBanting and Best Department of Medical Research, University of Toronto, Toronto, ON M5S 3E1, Canada;

    rnBeijing NMR Center, Peking University, Beijing 100871, China;

    rnDepartment of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada;

    rnBeijing NMR Center, Peking University, Beijing 100871, China School of Life Sciences, Peking University, Beijing 100871, China College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China;

    rnDepartment of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada;

  • 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

    H-NS; virulence;

    机译:H-NS;毒力;

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