Cobalt stress in Escherichia coli. The effect on the iron-sulfur proteins.
Cobalt is toxic for cells, but mechanisms of this toxicity are largely unknown. The biochemical and genetic experiments reported here demonstrate that iron-sulfur proteins are greatly affected in cobalt-treated Escherichia coli cells. Exposure of a wild-type strain to intracellular cobalt results in the inactivation of three selected iron-sulfur enzymes, the tRNA methylthio-transferase, aconitase, and ferrichrome reductase. Consistently, mutant strains lacking the [Fe-S] cluster assembly SUF machinery are hypersensitive to cobalt. Last, expression of iron uptake genes is increased in cells treated with cobalt. In vitro studies demonstrated that cobalt does not react directly with fully assembled [Fe-S] clusters. In contrast, it reacts with labile ones present in scaffold proteins (IscU, SufA) involved in iron-sulfur cluster biosynthesis. We propose a model wherein cobalt competes out iron during synthesis of [Fe-S] clusters in metabolically essential proteins.
Ranquet
Caroline
C
Laboratoire de Chimie et Biologie des Métaux, iRTSV/LCBM, Commissariat à l'Energie Atomique/CNRS/Université Joseph Fourier, CEA-Grenoble, UMR 5249, 17 Avenue des Martyrs, 38054 Grenoble Cedex 09, France.
Ollagnier-de-Choudens
Sandrine
S
Loiseau
Laurent
L
Barras
Frédéric
F
Fontecave
Marc
M
D000154:Aconitate Hydratase / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D003035:Cobalt / Q000633:toxicity*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D007506:Iron-Sulfur Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D013455:Sulfur / Q000378:metabolism; D013466:Sulfurtransferases / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D029968:Escherichia coli Proteins; D007506:Iron-Sulfur Proteins; C411665:IscU protein, E coli; C499169:SufA protein, E coli; D003035:Cobalt; D013455:Sulfur; D007501:Iron; D010088:Oxidoreductases; C010421:ferrichrome reductase; D013466:Sulfurtransferases; C023200:tRNA sulfurtransferase; D000154:Aconitate Hydratase