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The Zinc-Responsive Regulator Zur Controls a Zinc Uptake System and Some Ribosomal Proteins in Streptomyces coelicolor A3(2)

Laboratory of Molecular Microbiology, School of Biological Sciences, and Institute of Microbiology, Seoul National University, Seoul 151-742, Korea,¹ Department of Chemistry, Mokpo National University, Muan, Korea²

Received 11 December 2006/ Accepted 23 March 2007

In various bacteria, Zur, a zinc-specific regulator of the Fur family, regulates genes for zinc transport systems to maintain zinc homeostasis. It has also been suggested that Zur controls zinc mobilization by regulating some ribosomal proteins. The antibiotic-producing soil bacterium Streptomyces coelicolor contains four genes for Fur family regulators, and one (named zur) is located downstream of the znuACB operon encoding a putative zinc uptake transporter. We found that zinc specifically repressed the level of znuA transcripts and that this level was derepressed in a zur mutant. Purified Zur existing as homodimers bound to the znuA promoter region in the presence of zinc, confirming the role of Zur as a zinc-responsive repressor. We analyzed transcripts for paralogous forms of ribosomal proteins L31 (RpmE1 and RpmE2) and L33 (RpmG2 and RpmG3) for their dependence on Zur and found that RpmE2 and RpmG2 with no zinc-binding motif of conserved cysteines (C's) were negatively regulated by Zur. C-negative RpmG3 and C-positive RpmE1 were not regulated by Zur. Instead, they were regulated by the sigma factor ^R as predicted from their promoter sequences. The rpmE1 and rpmG3 genes were partially induced by EDTA in a manner dependent on ^R, suggesting that zinc depletion may stimulate the ^R regulatory system. This finding reflects a link between thiol-oxidizing stress and zinc depletion. We determined the Zur-binding sites within znuA and rpmG2 promoter regions by footprinting analyses and identified a consensus inverted repeat sequence (TGaaAatgatTttCA, where uppercase letters represent the nucleotides common to all sites analyzed). This sequence closely matches that for mycobacterial Zur and allows the prediction of more genes in the Zur regulon.

Published ahead of print on 6 April 2007.

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