Mycobacterium tuberculosis WhiB1 is an essential DNA-binding protein with a nitric oxide-sensitive iron-sulfur cluster.
Mycobacterium tuberculosis WhiB1 is an essential DNA-binding protein with a nitric oxide-sensitive iron-sulfur cluster.
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DOI：
10.1042/bj20101440
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发表时间：
2010-12-15
期刊：
影响因子：
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通讯作者：
Green J
中科院分区：
文献类型：
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作者：
Smith LJ;Stapleton MR;Fullstone GJ;Crack JC;Thomson AJ;Le Brun NE;Hunt DM;Harvey E;Adinolfi S;Buxton RS;Green J
结核分枝杆菌是一种主要病原体，具有建立和摆脱持续状态的能力。Wbl家族蛋白与放线菌的发育过程有关，M.结核病有七种这样的蛋白质。这里表明，M。结核病H37 Rv whiB 1基因是必需的。WhiB 1蛋白具有一个[4Fe-4S]2+簇，该簇在空气中稳定，但与8当量的一氧化氮快速反应，产生两个双核二亚硝酰基-硫醇铁络合物。WhiB 1的[4Fe-4S]形式不结合whiB 1启动子DNA，但还原和氧化的apo-WhiB 1和一氧化氮处理的holo-WhiB 1结合DNA。耻垢分枝杆菌RNA聚合酶在体外诱导whiB 1的转录;然而，在存在apo-WhiB 1的情况下，转录被严重抑制，无论是否存在CRP蛋白Rv 3676，这是已知的激活whiB 1表达。足迹法表明，自阻遏whiB 1是通过apo-WhiB 1结合在一个区域，重叠的核心启动子元件。一个模型，将调节whiB 1的表达响应一氧化氮和cAMP的影响进行了讨论，在建立M。肺结核感染。
Mycobacterium tuberculosis is a major pathogen that has the ability to establish, and emerge from, a persistent state. Wbl family proteins are associated with developmental processes in actinomycetes, and M. tuberculosis has seven such proteins. Here it is shown that the M. tuberculosis H37Rv whiB1 gene is essential. The WhiB1 protein possesses a [4Fe-4S]2+ cluster that is stable in air but reacts rapidly with eight equivalents of nitric oxide to yield two dinuclear dinitrosyl-iron thiol complexes. The [4Fe-4S] form of WhiB1 did not bind whiB1 promoter DNA, but the reduced and oxidized apo-WhiB1, and nitric oxide-treated holo-WhiB1 did bind to DNA. Mycobacterium smegmatis RNA polymerase induced transcription of whiB1 in vitro; however in the presence of apo-WhiB1 transcription was severely inhibited, irrespective of the presence or absence of the CRP protein Rv3676, which is known to activate whiB1 expression. Footprinting suggested that autorepression of whiB1 is achieved by apo-WhiB1 binding at a region that overlaps the core promoter elements. A model incorporating regulation of whiB1 expression in response to nitric oxide and cAMP is discussed with implications for sensing two important signals in establishing M. tuberculosis infections.