Regulation of iron-sulphur cluster homeostasis through transcriptional control of the Isc pathway by [2Fe-2S]-IscR in Escherichia coli.
Fe-S clusters are essential across the biological world, yet how cells regulate expression of Fe-S cluster biogenesis pathways to cope with changes in Fe-S cluster demand is not well understood. Here, we describe the mechanism by which IscR, a [2Fe-2S] cluster-containing regulator of Escherichia coli, adjusts the synthesis of the Isc Fe-S biogenesis pathway to maintain Fe-S homeostasis. Our data indicate that a negative feedback loop operates to repress transcription of the iscRSUA-hscBA-fdx operon, encoding IscR and the Isc machinery, through binding of [2Fe-2S]-IscR to two upstream binding sites. IscR was shown to require primarily the Isc pathway for synthesis of its Fe-S cluster, providing a link between IscR activity and demands for Fe-S clusters through the levels of the Isc system. Surprisingly, the isc operon was more repressed under anaerobic conditions, indicating increased Fe-S cluster occupancy of IscR and decreased Fe-S cluster biogenesis demand relative to aerobic conditions. Consistent with this notion, overexpression of a Fe-S protein under aerobic conditions, but not under anaerobic conditions, led to derepression of P(iscR). Together, these data show how transcriptional control of iscRSUA-hscBA-fdx by [2Fe-2S]-IscR allows E. coli to respond efficiently to varying Fe-S demands.
Microbiology Doctoral Training Program, University of Wisconsin, Madison, WI 53706, USA.
Jennifer L
JL
Giel
April D
AD
Nesbit
Erin L
EL
Mettert
Angela S
AS
Fleischhacker
Brendan T
BT
Wanta
Patricia J
PJ
Kiley
D000332:Aerobiosis; D000693:Anaerobiosis; D004269:DNA, Bacterial / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D025461:Feedback, Physiological; D015964:Gene Expression Regulation, Bacterial; D006706:Homeostasis; D007501:Iron / Q000378:metabolism*; D009876:Operon; D011485:Protein Binding; D012045:Regulatory Sequences, Nucleic Acid; D013455:Sulfur / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; C499695:IscR protein, E coli; D014157:Transcription Factors; D013455:Sulfur; D007501:Iron