The hydH/G Genes from Escherichia coli code for a zinc and lead responsive two-component regulatory system

J Mol Biol. 2001 Mar 16;307(1):93-105. doi: 10.1006/jmbi.2000.4451.


The hydH/G genes from Escherichia coli code for a two-component regulatory system that has been implicated in the regulation of hydrogenase 3 formation. In a detailed study of the function of HydH/G employing hycA'-'lacZ reporter gene fusions, it was shown that HydH/G indeed led to a stimulation of activation of the hycA promoter responsible for hydrogenase 3 synthesis but only when hydG is overexpressed from a plasmid in a strain lacking FhlA. Since the stimulation was not observed with an fdhF'-'lacZ fusion, and since it was independent from a functional hydH gene product, it must be considered as unspecific cross-talk. An extensive search for the actual physiological signal of HydH/G showed that the system responds to high concentrations of zinc or lead in the medium. Expression of zraP, a gene inversely oriented to hydH/G whose product seems to be involved in acquisition of tolerance to high Zn(2+) concentrations, is stimulated by high Zn(2+) and Pb(2+) concentrations and this stimulation requires both HydH and HydG. Purified HydG in the presence of phosphoryl donors binds to a region within the zraP-hydHG intergenic region that is characterised by two inverted repeats separated by a 14 bp spacer. Putative -12/-24 sigma(54)-dependent promoter motifs are present upstream of both the zraP and the hydHG transcriptional units; in accordance, transcription of zraP is strictly dependent on the presence of a functional rpoN gene. The expression of hydH/G is autoregulated: high Zn(2+) and Pb(2+) concentrations lead to a significant increase of the HydG protein content which took place only in a hydH(+) genetic background. Since HydH binds to membranes tightly, it is assumed that the HydH/G system senses high periplasmic Zn(2+) and Pb(2+) concentrations and contributes to metal tolerance by activating the expression of zraP. The redesignation of hydH/G as zraS/R is suggested.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Bacterial Proteins / physiology
  • Base Sequence
  • Cloning, Molecular
  • DNA Footprinting
  • DNA, Bacterial / analysis
  • DNA, Bacterial / metabolism
  • DNA-Binding Proteins*
  • DNA-Directed RNA Polymerases / physiology
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism
  • Escherichia coli Proteins*
  • Formate Dehydrogenases / genetics
  • Gene Expression Regulation, Bacterial
  • Hydrogenase / genetics
  • Lead / metabolism*
  • Molecular Sequence Data
  • Molecular Weight
  • Multienzyme Complexes / genetics
  • RNA Polymerase Sigma 54
  • Sequence Homology, Nucleic Acid
  • Sigma Factor / physiology
  • Trans-Activators / genetics*
  • Trans-Activators / physiology
  • Transcription, Genetic
  • Zinc / metabolism*


  • Bacterial Proteins
  • DNA, Bacterial
  • DNA-Binding Proteins
  • Escherichia coli Proteins
  • Multienzyme Complexes
  • Sigma Factor
  • Trans-Activators
  • rpoN protein, E coli
  • zraP protein, E coli
  • zraR protein, E coli
  • zraS protein, E coli
  • Lead
  • Hydrogenase
  • Formate Dehydrogenases
  • formate hydrogenlyase
  • DNA-Directed RNA Polymerases
  • RNA Polymerase Sigma 54
  • Zinc