Zinc-dependent regulation of zinc import and export genes by Zur

Seung-Hwan Choi,Jung-Hye Roe,Sun-Shin Cha,Yoo-Bok Cho,Jung-Ho Shin,Kang-Lok Lee

doi:10.1038/ncomms15812

Seung-Hwan Choi, Jung-Hye Roe + Show 4 more

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https://doi.org/10.1038/ncomms15812

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Abstract

In most bacteria, zinc depletion is sensed by Zur, whereas the surplus is sensed by different regulators to achieve zinc homeostasis. Here we present evidence that zinc-bound Zur not only represses genes for zinc acquisition but also induces the zitB gene encoding a zinc exporter in Streptomyces coelicolor, a model actinobacteria. Zinc-dependent gene regulation by Zur occurs in two phases. At sub-femtomolar zinc concentrations (phase I), dimeric Zur binds to the Zur-box motif immediately upstream of the zitB promoter, resulting in low zitB expression. At the same time, Zur represses genes for zinc uptake. At micromolar zinc concentrations (phase II), oligomeric Zur binding with footprint expansion upward from the Zur box results in high zitB induction. Our findings reveal a mode of zinc-dependent gene activation that uses a single metalloregulator to control genes for both uptake and export over a wide range of zinc concentrations.

Highlights

In most bacteria, zinc depletion is sensed by Zur, whereas the surplus is sensed by different regulators to achieve zinc homeostasis
In Escherichia coli, where zinc homeostasis is best studied, the uptake regulator Zur was reported to respond to low level of ‘free’ cytoplasmic buffered zinc, in femtomolar range[13], whereas the efflux regulator ZntR responds to free zinc of femtomolar to nanomolar range[13,14]
This study reveals the mode of achieving zinc homeostasis by Zur that binds to both import and export genes at the Zur-box sequences, and exerts a repressor or an activator function over a wide range of zinc concentrations

Summary

Introduction

Zinc depletion is sensed by Zur, whereas the surplus is sensed by different regulators to achieve zinc homeostasis. Our findings reveal a mode of zinc-dependent gene activation that uses a single metalloregulator to control genes for both uptake and export over a wide range of zinc concentrations. Transition metals such as iron, zinc, copper and manganese are key constituents of the cell but are toxic when in excess. This study reveals the mode of achieving zinc homeostasis by Zur that binds to both import and export genes at the Zur-box sequences, and exerts a repressor or an activator function over a wide range of zinc concentrations

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