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The FeoC [4Fe4S] Cluster Is Redox-Active and Rapidly Oxygen-Sensitive



Aaron T. Smith, Richard O. Linkous, Nathan Max, Alexandrea E. Sestok, Veronika Szalai, Kelly N. Chacon


The acquisition of iron is essential to establishing virulence among most pathogens. Under acidic and/or anaerobic conditions, most bacteria utilize the widely-distributed ferrous iron (Fe2+) uptake (Feo) system to import metabolically-required iron. The Feo system is inadequately understood at the atomic, molecular, and mechanistic levels, but we do know it is comprised of a main membrane component (FeoB) essential for iron translocation, as well as two small, cytosolic proteins (FeoA and FeoC) hypothesized to function as accessories to this process. FeoC has many hypothetical functions, including that of an iron-responsive transcriptional regulator. Here, we demonstrate for the first time that Escherichia coli FeoC (EcFeoC) binds an [Fe-S] cluster. Using electronic absorption, X-ray absorption, and electron paramagnetic resonance spectroscopies, we extensively characterize the nature of this cluster. Under strictly anaerobic conditions after chemical reconstitution, we demonstrate that EcFeoC binds a redox-active [4Fe-4S]2+/+ cluster that is rapidly oxygen-sensitive (t½ ≈ 20 s), similar to the [Fe-S] cluster in the fumarate and nitrate reductase (FNR) transcriptional regulator. In a manner similar to FNR, we further probed the nature of the oxygen-induced cluster decay products and report conversion of a [4Fe-4S]2+ cluster to a [2Fe-2S]2+ cluster. In contrast to FNR, we show that [4Fe-4S]2+ cluster binding to EcFeoC is associated with modest conformational changes of the polypeptide, but not protein dimerization. Finally, we posit a working hypothesis in which the cluster-binding FeoCs may function as oxygen-sensitive iron sensors that fine-tune pathogenic ferrous iron acquisition.


iron sulfur cluster, epr spectroscopy, XAS, bacterial virulence


Smith, A. , Linkous, R. , Max, N. , Sestok, A. , Szalai, V. and Chacon, K. (2019), The FeoC [4Fe4S] Cluster Is Redox-Active and Rapidly Oxygen-Sensitive, Biochemistry, [online],, (Accessed April 16, 2024)
Created November 11, 2019, Updated October 12, 2021