Structure-function relationships of the NsrR and RsrR transcription regulators

Anne Volbeda, Jason C. Crack, Nick Le Brun, Juan C. Fontecilla-Camps

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Protein-coordinated iron–sulfur clusters play multiple crucial functions in biological processes. One of these functions is the response to effectors that regulate gene expression. This response can be very variable. Several members of the Rrf2 family of bacterial transcriptional regulators contain [FeS] clusters that perform a variety of sensing roles, including those involved in controlling cellular iron levels (RirA), controlling [FeS] cluster synthesis (IscR), responding to nitrosative stress (NsrR), and monitoring and possibly regulating the redox status of the cell (RsrR). Cluster ligation and composition varies significantly, and, with the exception of RsrR, DNA binding is regulated by effector-dependent either partial or total cluster disassembly. Our own recent work has concentrated on the structure–function relationships of NsrR and RsrR, which coordinate [4Fe4S] and [2Fe2S] clusters, respectively. The reaction of nitric oxide with the NsrR [4Fe4S] cluster is progressive and modulates NsrR binding to different promotors. One consequence of cluster disassembly is the disruption of a key salt bridge that, in turn, causes a conformational change in the helix-turn-helix DNA-binding domain of NsrR. The case of RsrR is especially interesting because its DNA binding depends on a one-electron cluster redox change. This reduction causes the protonation of a neighboring His residue, which is followed by the generation of a protein cavity and the rotation of a tryptophan residue into it. Like in the case of NsrR, this rotation provokes a conformational change in the helix-turn-helix DNA-binding domain of the protein.
Original languageEnglish
Title of host publicationEncyclopedia of Inorganic and Bioinorganic Chemistry
EditorsR. A. Scott
PublisherWiley
DOIs
Publication statusPublished - 2023

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