Signal perception by FNR: the role of the iron–sulfur cluster

Jason C. Crack, Adrian J. Jervis, Alice Gaskell, Gaye F. White, Jeffrey Green, Andrew J. Thomson, Nick E. Le Brun

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)


The metabolic flexibility of bacteria is key to their ability to survive and thrive in a wide range of environments. Optimal switching from one metabolic pathway to another is a key requirement for this flexibility. Respiration is a good example: many bacteria utilize O2 as the terminal electron acceptor, but can switch to a range of other acceptors, such as nitrate, when O2 becomes limiting. Sensing environmental levels of O2 is the key step in switching from aerobic to anaerobic respiration. In Escherichia coli, the fumarate and nitrate reduction transcriptional regulator (FNR) controls this switch. Under O2-limiting conditions, FNR binds a [4Fe–4S]2+ cluster, generating a transcriptionally active dimeric form. Exposure to O2 results in conversion of the cluster into a [2Fe–2S]2+ form, leading to dissociation of the protein into inactive monomers. The mechanism of cluster conversion, together with the nature of the reaction products, is of considerable current interest, and a near-complete description of the process has now emerged. The [4Fe–4S]2+ into [2Fe–2S]2+ cluster conversion proceeds via a two-step mechanism. In step 1, a one-electron oxidation of the cluster takes place, resulting in the release of a Fe2+ ion, the formation of an intermediate [3Fe–4S]1+ cluster, together with the generation of a superoxide anion. In step 2, the intermediate [3Fe–4S]1+ cluster rearranges spontaneously to form the [2Fe–2S]2+ cluster, releasing two sulfide ions and an Fe3+ ion in the process. The one-electron activation of the cluster, coupled to catalytic recycling of the superoxide anion back to oxygen via superoxide dismutase and catalase, provides a novel means of amplifying the sensitivity of [4Fe–4S]2+ FNR to its signal molecule.
Original languageEnglish
Pages (from-to)1144–1148
Number of pages5
JournalBiochemical Society Transactions
Issue number6
Publication statusPublished - 2008

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