Allosteric regulation of the nickel-responsive NikR transcription factor from Helicobacter pylori.

The Journal of Biological Chemistry
Karina A BakshDeborah B Zamble

Abstract

Nickel is essential for the survival of the pathogenic bacteria Helicobacter pylori in the fluctuating pH of the human stomach. Due to its inherent toxicity and limited availability, nickel homeostasis is maintained through a network of pathways that are coordinated by the nickel-responsive transcription factor NikR. Nickel binding to H. pylori NikR (HpNikR) induces an allosteric response favoring a conformation that can bind specific DNA motifs, thereby serving to either activate or repress transcription of specific genes involved in nickel homeostasis and acid adaptation. Here, we examine how nickel induces this response using 19F-NMR, which reveals conformational and dynamic changes associated with nickel-activated DNA complex formation. HpNikR adopts an equilibrium between an open state and DNA-binding competent states regardless of nickel binding, but a higher level of dynamics is observed in the absence of metal. Nickel binding shifts the equilibrium toward the binding-competent states and decreases the mobility of the DNA-binding domains. The nickel-bound protein is then able to adopt a single conformation upon binding a target DNA promoter. Zinc, which does not promote high-affinity DNA binding, is unable to induce the ...Continue Reading

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