title: IscR of Rhodobacter sphaeroides functions as repressor of genes for iron-sulfur metabolism and represents a new type of iron-sulfur-binding protein.
abstract: IscR proteins are known as transcriptional regulators for Fe-S biogenesis. In the facultatively phototrophic bacterium, Rhodobacter sphaeroides IscR is the product of the first gene in the isc-suf operon. A major role of IscR in R. sphaeroides iron-dependent regulation was suggested in a bioinformatic study (Rodionov et al., PLoS Comput Biol 2:e163, 2006), which predicted a binding site in the upstream regions of several iron uptake genes, named Iron-Rhodo-box. Most known IscR proteins have Fe-S clusters featuring (Cys)3 (His)1 ligation. However, IscR proteins from Rhodobacteraceae harbor only a single-Cys residue and it was considered unlikely that they can ligate an Fe-S cluster. In this study, the role of R. sphaeroides IscR as transcriptional regulator and sensor of the Fe-S cluster status of the cell was analyzed. A mutant lacking IscR is more impaired in growth under iron limitation than the wild-type and exhibits significantly increased ROS levels in iron-replete and iron-deplete conditions. Expression studies reveal that R. sphaeroides IscR in its cluster-bound form functions as transcriptional repressor of genes involved in iron metabolism by direct binding to the promoter region of genes preceded by the motif. A total of 110 genes are directly or indirectly affected by IscR. Furthermore, IscR possesses a unique Fe-S cluster ligation scheme with only a single cysteine involved.
authors.affiliation: Institut für Mikrobiologie und Molekularbiologie, IFZ, Justus-Liebig-Universität, 35392, Giessen, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Remes
authors.affiliation: Institut für Mikrobiologie und Molekularbiologie, IFZ, Justus-Liebig-Universität, 35392, Giessen, Germany.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Eisenhardt
authors.affiliation: LOEWE-Zentrum für Synthetische Mikrobiologie, Philipps Universität Marburg, 35043, Marburg, Germany.
authors.forename: Vasundara
authors.initials: V
authors.lastname: Srinivasan
authors.affiliation: Institut für Mikrobiologie und Molekularbiologie, IFZ, Justus-Liebig-Universität, 35392, Giessen, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Klug
mesh_terms: D003470:Culture Media / Q000737:chemistry; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D007501:Iron / Q000378:metabolism; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017382:Reactive Oxygen Species / Q000032:analysis; D018085:Regulon; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D012242:Rhodobacter sphaeroides / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D017422:Sequence Analysis, DNA
chemical_list: D003470:Culture Media; D004269:DNA, Bacterial; D007506:Iron-Sulfur Proteins; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; D007501:Iron
keywords: Fe-S proteins; Iron-Rhodo-box; IscR; Rhodobacter sphaeroides; iron; iron-sulfur cluster