Department of Biochemistry, State University of New York, Buffalo, NY 14214, USA.
Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10691-5. doi: 10.1073/pnas.1002342107. Epub 2010 May 24.
Perception and response to nutritional iron availability by bacteria are essential to control cellular iron homeostasis. The Irr protein from Bradyrhizobium japonicum senses iron through the status of heme biosynthesis to globally regulate iron-dependent gene expression. Heme binds directly to Irr to trigger its degradation. Here, we show that severe manganese limitation created by growth of a Mn(2+) transport mutant in manganese-limited media resulted in a cellular iron deficiency. In wild-type cells, Irr levels were attenuated under manganese limitation, resulting in reduced promoter occupancy of target genes and altered iron-dependent gene expression. Irr levels were high regardless of manganese availability in a heme-deficient mutant, indicating that manganese normally affects heme-dependent degradation of Irr. Manganese altered the secondary structure of Irr in vitro and inhibited binding of heme to the protein. We propose that manganese limitation destabilizes Irr under low-iron conditions by lowering the threshold of heme that can trigger Irr degradation. The findings implicate a mechanism for the control of iron homeostasis by manganese in a bacterium.
细菌对营养铁可用性的感知和反应对于控制细胞内铁稳态至关重要。来自大豆根瘤菌的 Irr 蛋白通过血红素生物合成的状态来感知铁，从而全局调节铁依赖性基因表达。血红素直接与 Irr 结合以触发其降解。在这里，我们表明，在锰有限培养基中生长锰转运突变体导致严重的锰限制，从而导致细胞内铁缺乏。在野生型细胞中，锰限制下 Irr 水平降低，导致靶基因启动子占有率降低和铁依赖性基因表达改变。在血红素缺陷突变体中，无论锰的可用性如何，Irr 水平都很高，表明锰通常会影响血红素依赖性 Irr 降解。锰在体外改变了 Irr 的二级结构并抑制了血红素与蛋白质的结合。我们提出，在低铁条件下，锰限制通过降低触发 Irr 降解的血红素阈值来破坏 Irr 的稳定性。这些发现表明，在细菌中，锰通过一种机制来控制铁稳态。
