Insights into the Rrf2 repressor family - the structure of CymR, the global cysteine regulator of Bacillus subtilis

Insights into the Rrf2 repressor family - the structure of CymR, the global cysteine regulator of Bacillus subtilis
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DOI:
10.1111/j.1742-4658.2011.08195.x
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发表时间:
2011-08-01
期刊:
影响因子:
5.4
通讯作者:
Martin-Verstraete, Isabelle
Martin-Verstraete, Isabelle
中科院分区:
生物学2区
文献类型:
--
作者:
Shepard, William;Soutourina, Olga;Martin-Verstraete, Isabelle

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全球调控因子Cymr抑制枯草芽孢杆菌和金黄色葡萄球菌中与半胱氨酸摄取和半胱氨酸生物合成有关的一大组基因的转录。这个抑制子属于分布广泛但特性不佳的Rrf2调节蛋白家族。枯草杆菌CymR的晶体结构揭示了一个具有生物活性的二聚体,其中每个单体折叠成两个紧密排列的结构域:一个DNA结合结构域,其中包含一个有翼的螺旋-转角螺旋(WHTH)基序;以及一个长的二聚结构域,它将wHTH基序放置在两端。这种架构解释了这些小型调节器如何跨越23-27个碱基对的DNA目标。Cymr的wHTH基序类似于GntR超家族监管机构,如FadR和HutC。将FadR wHTH基序与其DNA片段结合在CymR二聚体结构的wHTH基序上,表明DNA靶和/或蛋白质在结合时必须经历一些构象变化。Cymr结构还暗示了与几个RRF2型调节因子相关的Fe-S中心的可能位置。
The global regulator CymR represses the transcription of a large set of genes involved in cystine uptake and cysteine biosynthesis in Bacillus subtilis and Staphylococcus aureus. This repressor belongs to the widespread and poorly characterized Rrf2 family of regulators. The crystal structure of CymR from B. subtilis reveals a biologically active dimer, where each monomer folds into two tightly packed domains: a DNA-binding domain, which houses a winged helix-turn-helix (wHTH) motif; and a long dimerization domain, which places the wHTH motifs at the extremes. This architecture explains how these small regulators can span 23-27-bp DNA targets. The wHTH motif of CymR resembles those of the GntR superfamily of regulators, such as FadR and HutC. Superimposing the FadR wHTH motifs bound to their DNA fragments onto the wHTH motifs of the CymR dimer structure suggests that the DNA target and/or the protein must undergo some conformational changes upon binding. The CymR structure also hints at a possible location of the Fe-S centre associated with several Rrf2-type regulators.