Structural and mechanistic insights into Helicobacter pylori NikR activation

C. Bahlawane, C. Dian, C. Muller, A. Round, C. Fauquant, K. Schauer, H. de Reuse, L. Terradot, I. Michaud-Soret*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

34 Citations (Scopus)


NikR is a transcriptional metalloregulator central in the mandatory response to acidity of Helicobacter pylori that controls the expression of numerous genes by binding to specific promoter regions. NikR/DNA interactions were proposed to rely on protein activation by Ni(II) binding to high-affinity (HA) and possibly secondary external (X) sites. We describe a biochemical characterization of HpNikR mutants that shows that the HA sites are essential but not sufficient for DNA binding, while the secondary external (X) sites and residues from the HpNikR dimer-dimer interface are important for DNA binding. We show that a second metal is necessary for HpNikR/DNA binding, but only to some promoters. Small-angle X-ray scattering shows that HpNikR adopts a defined conformation in solution, resembling the cis-conformation and suggests that nickel does not trigger large conformational changes in HpNikR. The crystal structures of selected mutants identify the effects of each mutation on HpNikR structure. This study unravels key structural features from which we derive a model for HpNikR activation where: (i) HA sites and an hydrogen bond network are required for DNA binding and (ii) metallation of a unique secondary external site (X) modulates HpNikR DNA binding to low-affinity promoters by disruption of a salt bridge.

Original languageEnglish
Article numbergkp1216
Pages (from-to)3106-3118
Number of pages13
JournalNucleic Acids Research
Issue number9
Publication statusPublished - 16 Jan 2010
Externally publishedYes


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