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Structural Changes in the Nickel‐Responsive Regulator NikR from Helicobacter pylori
Author(s) -
Baksh Karina Amelia,
Wong Jeremy,
Pham Tamara,
Zamble Deborah Beth
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.603.17
Subject(s) - helicobacter pylori , nickel , promoter , chemistry , hydrogenase , enzyme , transcription (linguistics) , transcription factor , biochemistry , urease , dna , mutant , gene , biology , gene expression , genetics , linguistics , philosophy , organic chemistry
Helicobacter pylori is a pathogenic bacterium estimated to infect 50% of the global population and causes peptic ulcers, gastritis, and gastric cancer. H. pylori is able to survive the fluctuating pH levels of the stomach mainly due to expression of two enzymes – urease and [NiFe]‐hydrogenase – that require nickel as an essential cofactor. Therefore, regulation of nickel concentration is crucial in order to avoid toxicity while maintaining an adequate supply. This is achieved by the nickel‐responsive transcription factor NikR (HpNikR), which maintains intracellular nickel homeostasis through binding the promoters of various genes, including those encoding nickel storage and import factors, and activating or repressing their transcription. HpNikR also plays a role in acid acclimation and there is evidence that its DNA‐binding activity can be modulated by changes in pH. It is therefore likely that there are promoter specific conformations exhibited by HpNikR that are sensitive to both nickel concentration and pH. However, the mechanisms by which nickel and pH activate DNA binding remain unclear. In this work, a series of mutants at key secondary structural elements were created as targets for labeling with a 19 F probe and 19 F‐NMR was used to uncover how nickel and pH influence the HpNikR conformational changes required for binding to different promoters. Support or Funding Information This work was supported in part by funding from the Canadian Institutes of Health Research.