title: Histidine residue 94 is involved in pH sensing by histidine kinase ArsS of Helicobacter pylori.
abstract: BACKGROUND
  The ArsRS two-component system is the master regulator of acid adaptation in the human gastric pathogen Helicobacter pylori. Low pH is supposed to trigger the autophosphorylation of the histidine kinase ArsS and the subsequent transfer of the phosphoryl group to its cognate response regulator ArsR which then acts as an activator or repressor of pH-responsive genes. Orthologs of the ArsRS two-component system are also present in H. pylori's close relatives H. hepaticus, Campylobacter jejuni and Wolinella succinogenes which are non-gastric colonizers.
  
  
  RESULTS
  In order to investigate the mechanism of acid perception by ArsS, derivatives of H. pylori 26695 expressing ArsS proteins with substitutions of the histidine residues present in its periplasmic input domain were constructed. Analysis of pH-responsive transcription of selected ArsRS target genes in these mutants revealed that H94 is relevant for pH sensing, however, our data indicate that protonatable amino acids other than histidine contribute substantially to acid perception by ArsS. By the construction and analysis of H. pylori mutants carrying arsS allels from the related epsilon-proteobacteria we demonstrate that WS1818 of W. succinogenes efficiently responds to acidic pH.
  
  
  CONCLUSIONS
  We show that H94 in the input domain of ArsS is crucial for acid perception in H. pylori 26695. In addition our data suggest that ArsS is able to adopt different conformations depending on the degree of protonation of acidic amino acids in the input domain. This might result in different activation states of the histidine kinase allowing a gradual transcriptional response to low pH conditions. Although retaining considerable similarity to ArsS the orthologous proteins of H. hepaticus and C. jejuni may have evolved to sensors of a different environmental stimulus in accordance with the non gastric habitat of these bacteria.
authors.affiliation: Theodor-Boveri-Institut für Biowissenschaften, Lehrstuhl für Mikrobiologie, Universität Würzburg, Am Hubland, Würzburg, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Müller
authors.forename: Monika
authors.initials: M
authors.lastname: Götz
authors.forename: Dagmar
authors.initials: D
authors.lastname: Beier
mesh_terms: D016123:Campylobacter jejuni / Q000378:metabolism; D044923:Helicobacter hepaticus / Q000378:metabolism; D016480:Helicobacter pylori / Q000378:metabolism*; D006639:Histidine / Q000737:chemistry* / Q000378:metabolism; D000071677:Histidine Kinase; D006863:Hydrogen-Ion Concentration; D008954:Models, Biological; D008957:Models, Genetic; D009154:Mutation; D016366:Open Reading Frames; D010766:Phosphorylation; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D013045:Species Specificity; D016968:Wolinella / Q000378:metabolism
chemical_list: D011993:Recombinant Fusion Proteins; D006639:Histidine; D011494:Protein Kinases; D000071677:Histidine Kinase