Transcriptional activation of an Escherichia coli copper efflux regulon by the chromosomal MerR homologue, cueR.
Because copper ions are both essential cofactors and cytotoxic agents, the net accumulation of this element in a cell must be carefully balanced. Depending upon the cellular copper status, copper ions must either be imported or ejected. CopA, the principal copper efflux ATPase in Escherichia coli, is induced by elevated copper in the medium, but the copper-sensing regulatory factor is unknown. Inspection of the copA promoter reveals signature elements of promoters controlled by metalloregulatory proteins in the MerR family. These same elements are also present upstream of yacK, which encodes a putative multi-copper oxidase. Homologues of YacK are found in copper resistance determinants that facilitate copper efflux. Here we show by targeted gene deletion and promoter fusion assays that both copA and yacK are regulated in a copper-responsive manner by the MerR homologue, ybbI. We have designated ybbI as cueR for the Cu efflux regulator. This represents the first example of a copper-responsive regulon on the E. coli chromosome and further extends the roles of MerR family members in prokaryotic stress response.
Department of Biochemistry, Molecular Biology, and Cell Biology and the Department of Chemistry, Northwestern University, Evanston, Illinois 60208, USA.
F W
FW
Outten
C E
CE
Outten
J
J
Hale
T V
TV
O'Halloran
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002876:Chromosomes, Bacterial; D003001:Cloning, Molecular; D003300:Copper / Q000378:metabolism*; D019327:Copper Sulfate / Q000494:pharmacology; D017931:DNA Primers / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D007477:Ions; D008969:Molecular Sequence Data; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017386:Sequence Homology, Amino Acid; D015533:Transcriptional Activation
D001426:Bacterial Proteins; C071263:CopA protein, Bacteria; D017931:DNA Primers; D004268:DNA-Binding Proteins; D007477:Ions; C051124:MerR protein, Bacteria; D003300:Copper; D019327:Copper Sulfate