The Bacillus subtilis iron-sparing response is mediated by a Fur-regulated small RNA and three small, basic proteins

The Bacillus subtilis iron-sparing response is mediated by a Fur-regulated small RNA and three small, basic proteins
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DOI:
10.1073/pnas.0711752105
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发表时间:
2008-08-19
影响因子:
11.1
通讯作者:
Helmann, John D.
Helmann, John D.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Gaballa, Ahmed;Antelmann, Haike;Helmann, John D.

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细菌铁稳态的调节通常由铁敏感铁摄取抑制子(Fur)控制。枯草芽孢杆菌皮毛蛋白作为铁载体生物合成和铁转运蛋白的铁依赖性阻遏物。在这里,我们表明,毛皮还协调一个节省铁的反应,其作用是抑制富铁蛋白质的表达时,铁是有限的。当毛皮失活时,许多含铁蛋白质被下调,包括琥珀酸脱氢酶、顺乌头酸酶、细胞色素和血红素、半胱氨酸和支链氨基酸的生物合成酶。因此,毛皮突变体在各种营养条件下生长缓慢。取决于生长培养基,快速生长可以通过铁节省反应的一个或多个分子效应子中的突变来恢复。这些效应子包括三个Fur调节的操纵子的产物,其编码小RNA(FsrA)和三个小的碱性蛋白质(FbpA、FbpB和FbpC)。FsrA和琥珀酸脱氢酶操纵子的前导区之间的广泛互补性与该靶点的RNA介导的翻译抑制机制一致。因此,B组缺铁。枯草杆菌激活途径以重塑蛋白质组,从而为最关键的细胞功能保留铁。
Regulation of bacterial iron homeostasis is often controlled by the iron-sensing ferric uptake repressor (Fur). The Bacillus subtilis Fur protein acts as an iron-dependent repressor for siderophore biosynthesis and iron transport proteins. Here, we demonstrate that Fur also coordinates an iron-sparing response that acts to repress the expression of iron-rich proteins when iron is limiting. When Fur is inactive, numerous iron-containing proteins are down-regulated, including succinate dehydrogenase, aconitase, cytochromes, and biosynthetic enzymes for heme, cysteine, and branched chain amino acids. As a result, a fur mutant grows slowly in a variety of nutrient conditions. Depending on the growth medium, rapid growth can be restored by mutations in one or more of the molecular effectors of the iron-sparing response. These effectors include the products of three Fur-regulated operons that encode a small RNA (FsrA) and three small, basic proteins (FbpA, FbpB, and FbpC). Extensive complementarity between FsrA and the leader region of the succinate dehydrogenase operon is consistent with an RNA-mediated translational repression mechanism for this target. Thus, iron deprivation in B. subtilis activates pathways to remodel the proteome to preserve iron for the most critical cellular functions.