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首页> 外文期刊>Biochemistry >Structure of the DNA-Binding Domain of the Response Regulator PhoP from Mycobacterium tuberculosis
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Structure of the DNA-Binding Domain of the Response Regulator PhoP from Mycobacterium tuberculosis

机译：结核分枝杆菌应答调节因子PhoP的DNA结合域的结构。

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The PhoP—PhoR two-component signaling system from Mycobacterium tuberculosis is essential for the virulence of the tubercle bacillus. The response regulator, PhoP, regulates expression of over 110 genes. In order to elucidate the regulatory mechanism of PhoP, we determined the crystal structure of its DNA-binding domain (PhoPC). PhoPC exhibits a typical fold of the winged helix—turn—helix subfamily of response regulators. The structure starts with a four-stranded antiparallel beta-sheet, followed by a three-helical bundle of alpha-helices, and then a C-terminal beta-hairpin, which together with a short beta-strand between the first and second helices forms a three-stranded antiparallel beta-sheet. Structural elements are packed through a hydrophobic core, with the first helix providing a scaffold for the rest of the domain to pack. The second and third helices and the long, flexible loop between them form the helix—turn—helix motif, with the third helix being the recognition helix. The C-terminal beta-hairpin turn forms the wing motif. The molecular surfaces around the recognition helix and the wing residues show strong positive electrostatic potential, consistent with their roles in DNA binding and nucleotide sequence recognition. The crystal packing of PhoPC gives a hexamer ring, with neighboring molecules interacting in a head-to-tail fashion. This packing interface suggests that PhoPC could bind DNA in a tandem association. However, this mode of DNA binding is likely to be nonspecific because the recognition helix is partially blocked and would be prevented from inserting into the major groove of DNA. Detailed structural analysis and implications with respect to DNA binding are discussed.
机译：结核分枝杆菌的PhoP-PhoR两组分信号系统对于结核杆菌的毒性至关重要。响应调节剂PhoP调节超过110个基因的表达。为了阐明PhoP的调控机制，我们确定了其DNA结合域（PhoPC）的晶体结构。 PhoPC表现出响应调节器的有翼螺旋-转-螺旋亚家族的典型折叠。结构以四链反平行β-折叠开始，然后是三螺旋α-螺旋束，然后是C末端β-发夹，在第一螺旋和第二螺旋之间形成短的β链三链反平行β-折叠。结构元件通过疏水核堆积，第一个螺旋结构为其余区域的堆积提供了支架。第二个和第三个螺旋以及它们之间的长而灵活的环形成了螺旋（转）螺旋基序，第三个螺旋是识别螺旋。 C端的β-发夹状转角形成机翼图案。识别螺旋和翼残基周围的分子表面显示出强的正静电势，与其在DNA结合和核苷酸序列识别中的作用一致。 PhoPC的晶体堆积产生一个六聚体环，相邻分子以头到尾的方式相互作用。这种包装界面表明PhoPC可以串联结合DNA。但是，这种DNA结合方式可能是非特异性的，因为识别螺旋被部分封闭，并且将防止插入到DNA的主要沟中。讨论了详细的结构分析和有关DNA结合的含义。

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