Escherichia Coli FeoC Binds a Redox-Active, Rapidly Oxygen-Sensitive [4Fe-4S] Cluster

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dc.contributor.authorSmith, Aaron T.
dc.contributor.authorLinkous, Richard O.
dc.contributor.authorMax, Nathan J.
dc.contributor.authorSestok, Alexandrea E.
dc.contributor.authorSzalai, Veronika A.
dc.contributor.authorChacón, Kelly N.
dc.date.accessioned2019-10-02T14:51:44Z
dc.date.available2019-10-02T14:51:44Z
dc.date.issued2019-02-07
dc.description.abstractThe 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⁺ᐟ⁺ cluster that is rapidly oxygen-sensitive (t₁/₂ ≈ 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.en_US
dc.description.sponsorshipThis work was supported by NSF CAREER grant 1844624 (A. T. S.), and in part by NIHNIGMS grant T32 GM066706 (A. E. S.). Sequence searches utilized both database and analysis functions of the Universal Protein Resource (UniProt) Knowledgebase and Reference Clusters (http://www.uniprot.org) and the National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov/). Use of the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract No. DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research, and by the National Institutes of Health, National Institute of General Medical Sciences (including P41 GM103393)en_US
dc.description.urihttps://chemrxiv.org/articles/Escherichia_Coli_FeoC_Binds_a_Redox-Active_Rapidly_Oxygen-Sensitive_4Fe-4S_Cluster/8411408/1en_US
dc.format.extent59 pagesen_US
dc.genreJournal Articlesen_US
dc.identifierdoi:10.13016/m20mqh-cwmm
dc.identifier.urihttp://hdl.handle.net/11603/14957
dc.language.isoen_USen_US
dc.relation.isAvailableAtThe University of Maryland, Baltimore County (UMBC)
dc.relation.ispartofUMBC Chemistry & Biochemistry Department Collection
dc.relation.ispartofUMBC Student Collection
dc.relation.ispartofUMBC Faculty Collection
dc.rightsThis item is likely protected under Title 17 of the U.S. Copyright Law. Unless on a Creative Commons license, for uses protected by Copyright Law, contact the copyright holder or the author.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)*
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectironen_US
dc.subjectsulfuren_US
dc.subjectclusteren_US
dc.subjectuptake transportersen_US
dc.subjectregulatorsen_US
dc.subjectFeoen_US
dc.titleEscherichia Coli FeoC Binds a Redox-Active, Rapidly Oxygen-Sensitive [4Fe-4S] Clusteren_US
dc.typeTexten_US

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