Wösten M M, Kox L F, Chamnongpol S, Soncini F C, Groisman E A
Department of Molecular Microbiology, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Cell. 2000 Sep 29;103(1):113-25. doi: 10.1016/s0092-8674(00)00092-1.
Iron is essential for all organisms but can be toxic in excess. Iron homeostasis is typically regulated by cytoplasmic iron binding proteins, but here we describe a signal transduction system (PmrA/PmrB) that responds to extracytoplasmic ferric iron. Iron promoted transcription of PmrA-activated genes and resistance to the antibiotic polymyxin in Salmonella. The PmrB protein bound iron via its periplasmic domain which harbors two copies of the sequence ExxE, a motif present in the Saccharomyces FTR1 iron transporter and in mammalian ferritin light chain. A pmrA mutant was hypersensitive to killing by iron but displayed wild-type resistance to a variety of oxidants, suggesting PmrA/PmrB controls a novel pathway mediating the avoidance of iron toxicity.
铁对所有生物体都至关重要，但过量时可能有毒。铁稳态通常由细胞质铁结合蛋白调节，但在此我们描述了一种响应胞外三价铁的信号转导系统（PmrA/PmrB）。铁促进了鼠伤寒沙门氏菌中PmrA激活基因的转录以及对抗生素多粘菌素的抗性。PmrB蛋白通过其周质结构域结合铁，该结构域含有两个ExxE序列拷贝，这是酿酒酵母FTR1铁转运蛋白和哺乳动物铁蛋白轻链中存在的一种基序。pmrA突变体对铁杀伤高度敏感，但对多种氧化剂表现出野生型抗性，这表明PmrA/PmrB控制着一条介导避免铁毒性的新途径。
