Lsr2 is a nucleoid-associated protein that targets AT-rich sequences and virulence genes in Mycobacterium tuberculosis
Lsr2 is a nucleoid-associated protein that targets AT-rich sequences and virulence genes in Mycobacterium tuberculosis
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DOI：
10.1073/pnas.0913551107
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发表时间：
2010-03-16
影响因子：
11.1
通讯作者：
Liu, Jun
中科院分区：
文献类型：
--
作者：
Gordon, Blair R. G.;Li, Yifei;Liu, Jun
细菌类核蛋白在染色体组构和基因调控中起着重要作用。我们发现，结核分枝杆菌的Lsr 2是一种独特的核苷相关蛋白，结合AT丰富的基因组区域，包括基因组岛获得的水平基因转移和区域编码的主要毒力因子，如ESX分泌系统，脂质毒力因子PDIM和PGL，和PE/PPE家族的抗原蛋白。全基因组结合数据与表达数据的比较表明Lsr 2结合导致转录抑制。结构域交换实验表明Lsr 2具有N端二聚化结构域和C端DNA结合结构域。对Lsr 2的DNA结合结构域及其与DNA的相互作用的核磁共振分析揭示了Lsr 2的独特结构和独特机制，该结构和机制使Lsr 2能够通过与DNA小沟的相互作用有区别地靶向富含AT的序列。总之，我们提供的证据表明，分枝杆菌采用了一种结构独特的分子，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，可能协调这组医学上重要的细菌的全球基因调控和毒力。
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.