Structural determinants of DNA recognition by the NO sensor NsrR and related Rrf2-type [FeS]-transcription factors.

Structural determinants of DNA recognition by the NO sensor NsrR and related Rrf2-type [FeS]-transcription factors.
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DOI:
10.1038/s42003-022-03745-7
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发表时间:
2022-07-30
影响因子:
5.9
通讯作者:
Volbeda, Anne
Volbeda, Anne
中科院分区:
生物学2区
文献类型:
--
作者:
Rohac, Roman;Crack, Jason C.;de Rosny, Eve;Gigarel, Oceane;Le Brun, Nick E.;Fontecilla-Camps, Juan C.;Volbeda, Anne

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Rrf2家族的几种转录因子使用铁-硫簇,通过一氧化氮(NO)、细胞氧化还原状态和铁水平等效应物来调节DNA结合。天蓝色链霉菌的[4Fe-4S]-NsrR(ScNsrR)通过与不同量的NO反应和形成复合体来调节三种不同基因的表达,从而导致这种气体的解毒。在这里,我们报道了与hmpA1基因操纵子片段复合的ScNsrR的晶体结构,并与以前报道的[2Fe-2S]-RsrR/rsrR和apo-Iscr/HYA复合体的晶体结构进行了比较。重要的结构差异在于DNA小槽和大槽宽度的变化。此外,还观察到不同的DNA曲线和不同的与蛋白质传感器的相互作用。我们还报道了NsrR与四个hmpA1变体结合的研究,这些研究表明中心区的灵活性不是关键的结合决定因素。我们的研究探索了三个密切相关的转录调控因子的启动子结合特异性。报道了天蓝色链霉菌铁硫蛋白NsrR与基因操纵子片段结合的晶体结构,并与其他结构进行了比较,揭示了NO传感器识别DNA的结构决定因素。
Several transcription factors of the Rrf2 family use an iron-sulfur cluster to regulate DNA binding through effectors such as nitric oxide (NO), cellular redox status and iron levels. [4Fe-4S]-NsrR from Streptomyces coelicolor (ScNsrR) modulates expression of three different genes via reaction and complex formation with variable amounts of NO, which results in detoxification of this gas. Here, we report the crystal structure of ScNsrR complexed with an hmpA1 gene operator fragment and compare it with those previously reported for [2Fe-2S]-RsrR/rsrR and apo-IscR/hyA complexes. Important structural differences reside in the variation of the DNA minor and major groove widths. In addition, different DNA curvatures and different interactions with the protein sensors are observed. We also report studies of NsrR binding to four hmpA1 variants, which indicate that flexibility in the central region is not a key binding determinant. Our study explores the promotor binding specificities of three closely related transcriptional regulators. The crystal structure of the iron-sulfur protein NsrR from Streptomyces coelicolor bound to a gene operator fragment is reported and compared with other structures, giving insight into the structural determinants of DNA recognition by the NO sensor.
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