Abstract

All organisms must regulate the cellular uptake, efflux, and intracellular trafficking of essential elements, including d-block metal ions. In bacteria, such regulation is achieved by the action of metal-responsive transcriptional regulators. Among several families of zinc-responsive transcription factors, the ‘zinc uptake regulator’ Zur is the most widespread. Zur normally represses transcription in its zinc-bound form, in which DNA-binding affinity is enhanced allosterically. Experimental and bioinformatic searches for Zur-regulated genes have revealed that in many cases, Zur proteins govern zinc homeostasis in a much more profound way than merely through the expression of uptake systems. Zur regulons also comprise biosynthetic clusters for metallophore synthesis, ribosomal proteins, enzymes, and virulence factors. In recognition of the importance of zinc homeostasis at the host–pathogen interface, studying Zur regulons of pathogenic bacteria is a particularly active current research area.

Highlights

  • For a long time, there has been a prevailing assumption that zinc is not a important element for prokaryotes

  • By governing the expression of zincsupplying and zinc-requiring proteins, they provide regulation of intracellular total and free Zn2+ concentrations. This protects bacteria against both high and low external Zn2+ concentrations, which is of particular interest regarding pathogens [7] and human microbiomes [102]

  • Protein folds are well conserved between zinc uptake regulator (Zur) proteins from different bacterial phyla, there is surprising diversity regarding the position of the sensory Zn-binding residues in the protein sequence

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Summary

Introduction

There has been a prevailing assumption that zinc is not a important element for prokaryotes. Activation assays involve studying the DNA-binding ability at different free Zn2+ concentrations; this can be monitored in vitro by EMSA, or by measuring in vivo transcription via a reporter gene under the control of a promoter containing the Zur box.

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