Harnessing toxic reactions to signal stress: Reactions of nitric oxide with iron-sulfur centers and the informative case of SoxR protein
Nitric oxide (NO) radicals provide a prominent pathway for disruption of iron-sulfur clusters, and lead to the formation of dinitrosyl-iron complexes (DNICs). In the case of the SoxR protein, this transformation converts the protein into a potent activator of gene transcription. SoxR is a homodimer protein containing a pair of [2Fe-2S] clusters, and it becomes activated when cells are exposed to superoxide or NO. Activation of this protein stimulates the transcription of the SoxR gene as a first step in a cascade to activate regulon promoters. Two distinct regulatory mechanisms have been recognized: First, regulation via the redox state since the protein is transcriptionally active only in oxidized state. Second, via the reversible assembly-disassembly of the [2Fe-2S] clusters. Although the DNICs formed in purified SoxR by treatment with pure NO gas are quite stable in vitro, the SoxR DNICs formed in intact cells are very rapidly replaced by normal reduced [2Fe-2S] centers, with a consequent deactivation of SoxR. The active repair of DNICs appears to be a general process that helps counteract the toxicity of NO exposure. The reversibility of the transformation FeS â†" DNIC also makes it well suited to a role in signal transduction. This chapter concentrates on a particular type of radical signaling by NO, namely the transformation of the FeS centers in SoxR to protein-bound DNICs. SoxR is unusual as the transformation activates the enzyme. This property is crucial for the role of SoxR as an oxidative stress regulator. In this protein, the reversible formation of DNIC provides an important mechanism for intracellular signaling. © 2007 Elsevier B.V. All rights reserved.
Publication Source (Journal or Book title)
Radicals for Life: The Various Forms of Nitric Oxide
Demple, B., Ding, H., Ren, B., & Reiter, T. (2007). Harnessing toxic reactions to signal stress: Reactions of nitric oxide with iron-sulfur centers and the informative case of SoxR protein. Radicals for Life: The Various Forms of Nitric Oxide, 147-160. https://doi.org/10.1016/B978-044452236-8/50007-1