iron sulfur proteins


Summary: A group of proteins possessing only the iron-sulfur complex as the prosthetic group. These proteins participate in all major pathways of electron transport: photosynthesis, respiration, hydroxylation and bacterial hydrogen and nitrogen fixation.

Top Publications

  1. Matos C, Robinson C, Di Cola A. The Tat system proofreads FeS protein substrates and directly initiates the disposal of rejected molecules. EMBO J. 2008;27:2055-63 pubmed publisher
  2. McGlynn S, Shepard E, Winslow M, Naumov A, Duschene K, Posewitz M, et al. HydF as a scaffold protein in [FeFe] hydrogenase H-cluster biosynthesis. FEBS Lett. 2008;582:2183-7 pubmed publisher
    ..These results represent the first in vitro maturation of [FeFe] hydrogenase with purified proteins, and suggest that HydF functions as a scaffold upon which an H-cluster intermediate is synthesized. ..
  3. Bernard D, Cheng Y, Zhao Y, Balk J. An allelic mutant series of ATM3 reveals its key role in the biogenesis of cytosolic iron-sulfur proteins in Arabidopsis. Plant Physiol. 2009;151:590-602 pubmed publisher
    ..Our data suggest that Arabidopsis ATM3 may transport (1) at least two distinct compounds or (2) a single compound required for both Fe-S and Moco assembly machineries in the cytosol, but not iron. ..
  4. Yu C, Cen X, Ma H, Yin Y, Yu L, Esser L, et al. Domain conformational switch of the iron-sulfur protein in cytochrome bc1 complex is induced by the electron transfer from cytochrome bL to bH. Biochim Biophys Acta. 2008;1777:1038-43 pubmed publisher
  5. Bandyopadhyay S, Chandramouli K, Johnson M. Iron-sulfur cluster biosynthesis. Biochem Soc Trans. 2008;36:1112-9 pubmed publisher
  6. Kumanovics A, Chen O, Li L, Bagley D, Adkins E, Lin H, et al. Identification of FRA1 and FRA2 as genes involved in regulating the yeast iron regulon in response to decreased mitochondrial iron-sulfur cluster synthesis. J Biol Chem. 2008;283:10276-86 pubmed publisher
    ..These results show that the Fra-Grx complex is an intermediate between the production of mitochondrial Fe-S clusters and transcription of the iron regulon. ..
  7. Kohbushi H, Nakai Y, Kikuchi S, Yabe T, Hori H, Nakai M. Arabidopsis cytosolic Nbp35 homodimer can assemble both [2Fe-2S] and [4Fe-4S] clusters in two distinct domains. Biochem Biophys Res Commun. 2009;378:810-5 pubmed publisher
    ..Taken together, our data suggest that Nbp35 plays a pivotal role in iron-sulfur cluster assembly and delivery in the plant cell cytosol as a bifunctional molecular scaffold. ..
  8. Shen G, Balasubramanian R, Wang T, Wu Y, Hoffart L, Krebs C, et al. SufR coordinates two [4Fe-4S]2+, 1+ clusters and functions as a transcriptional repressor of the sufBCDS operon and an autoregulator of sufR in cyanobacteria. J Biol Chem. 2007;282:31909-19 pubmed
    ..The Fe/S protein SufR thus functions both as a transcriptional repressor of the sufBCDS operon and as an autoregulator of sufR. ..
  9. Ye H, Jeong S, Ghosh M, Kovtunovych G, Silvestri L, Ortillo D, et al. Glutaredoxin 5 deficiency causes sideroblastic anemia by specifically impairing heme biosynthesis and depleting cytosolic iron in human erythroblasts. J Clin Invest. 2010;120:1749-61 pubmed publisher
    ..Erythroblasts express both IRP-repressible ALAS2 and non-IRP-repressible ferroportin 1b. The unique combination of IRP targets likely accounts for the tissue-specific phenotype of human GLRX5 deficiency...

More Information


  1. Raulfs E, O Carroll I, Dos Santos P, Unciuleac M, Dean D. In vivo iron-sulfur cluster formation. Proc Natl Acad Sci U S A. 2008;105:8591-6 pubmed publisher
    ..In aggregate, these results validate the scaffold hypothesis for [Fe-S] cluster assembly and indicate that in vivo [Fe-S] cluster formation is a dynamic process that involves the reversible interaction of IscU and IscS. ..
  2. Shimomura Y, Wada K, Fukuyama K, Takahashi Y. The asymmetric trimeric architecture of [2Fe-2S] IscU: implications for its scaffolding during iron-sulfur cluster biosynthesis. J Mol Biol. 2008;383:133-43 pubmed publisher
  3. Lill R, Muhlenhoff U. Maturation of iron-sulfur proteins in eukaryotes: mechanisms, connected processes, and diseases. Annu Rev Biochem. 2008;77:669-700 pubmed publisher
    ..Numerous diseases including several neurodegenerative and hematological disorders have been associated with defects in Fe/S protein biogenesis, underlining the central importance of this process for life. ..
  4. Cooley J, Lee D, Daldal F. Across membrane communication between the Q(o) and Q(i) active sites of cytochrome bc(1). Biochemistry. 2009;48:1888-99 pubmed publisher
  5. Lu J, Yang J, Tan G, Ding H. Complementary roles of SufA and IscA in the biogenesis of iron-sulfur clusters in Escherichia coli. Biochem J. 2008;409:535-43 pubmed
    ..The results suggest that SufA and IscA may constitute the redundant cellular activities to recruit intracellular iron and deliver iron for the iron-sulfur cluster assembly in E. coli. ..
  6. Tirrell T, Paddock M, Conlan A, Smoll E, Nechushtai R, Jennings P, et al. Resonance Raman studies of the (His)(Cys)3 2Fe-2S cluster of MitoNEET: comparison to the (Cys)4 mutant and implications of the effects of pH on the labile metal center. Biochemistry. 2009;48:4747-52 pubmed publisher
    ..These results support the hypothesis that the Fe-N(His87) interaction is modulated within the physiological pH range, and this modulation may be critical to the function of mitoNEET. ..
  7. Klinge S, Hirst J, Maman J, Krude T, Pellegrini L. An iron-sulfur domain of the eukaryotic primase is essential for RNA primer synthesis. Nat Struct Mol Biol. 2007;14:875-7 pubmed publisher
    ..We further show that the Fe-S domain is essential to the unique ability of the eukaryotic primase to start DNA replication...
  8. Paddock M, Wiley S, Axelrod H, Cohen A, Roy M, Abresch E, et al. MitoNEET is a uniquely folded 2Fe 2S outer mitochondrial membrane protein stabilized by pioglitazone. Proc Natl Acad Sci U S A. 2007;104:14342-7 pubmed
    ..The biophysical properties of mitoNEET suggest that it may participate in a redox-sensitive signaling and/or in Fe-S cluster transfer. ..
  9. Vogt S, Lyon E, Shima S, Thauer R. The exchange activities of [Fe] hydrogenase (iron-sulfur-cluster-free hydrogenase) from methanogenic archaea in comparison with the exchange activities of [FeFe] and [NiFe] hydrogenases. J Biol Inorg Chem. 2008;13:97-106 pubmed
    ..This differentiates [Fe] hydrogenase from [FeFe] and [NiFe] hydrogenases, which actively catalyze H2/H2O exchange in the absence of exogenous electron acceptors. ..
  10. Rouault T, Tong W. Iron-sulfur cluster biogenesis and human disease. Trends Genet. 2008;24:398-407 pubmed publisher
    ..Thus, defects in the iron-sulfur cluster biogenesis pathway could underlie many human diseases...
  11. Rothery R, Workun G, Weiner J. The prokaryotic complex iron-sulfur molybdoenzyme family. Biochim Biophys Acta. 2008;1778:1897-929 pubmed
    ..We have used genome sequence data to establish that there is a bias against the presence of soluble periplasmic molybdoenzymes in bacteria lacking an outer membrane...
  12. Hiromoto T, Ataka K, Pilak O, Vogt S, Stagni M, Meyer Klaucke W, et al. The crystal structure of C176A mutated [Fe]-hydrogenase suggests an acyl-iron ligation in the active site iron complex. FEBS Lett. 2009;583:585-90 pubmed publisher
    ..This result led to a re-interpretation of the iron ligation in the wild-type. ..
  13. Yabe T, Yamashita E, Kikuchi A, Morimoto K, Nakagawa A, Tsukihara T, et al. Structural analysis of Arabidopsis CnfU protein: an iron-sulfur cluster biosynthetic scaffold in chloroplasts. J Mol Biol. 2008;381:160-73 pubmed publisher
    ..We propose that such a structural framework is important for CnfU to function as a Fe-S cluster biosynthetic scaffold. ..
  14. Song D, Lee F. A role for IOP1 in mammalian cytosolic iron-sulfur protein biogenesis. J Biol Chem. 2008;283:9231-8 pubmed publisher
    ..IOP1 knockdown also leads to a decrease in activity of xanthine oxidase, a distinct cytosolic Fe-S protein. Taken together, these results provide evidence that IOP1 is involved in mammalian cytosolic Fe-S protein maturation. ..
  15. Goldberg A, Molik S, Tsaousis A, Neumann K, Kuhnke G, Delbac F, et al. Localization and functionality of microsporidian iron-sulphur cluster assembly proteins. Nature. 2008;452:624-8 pubmed publisher
    ..Together, our studies identify the essential biosynthetic process of Fe-S protein assembly as a key function of microsporidian mitosomes. ..
  16. Mettert E, Outten F, Wanta B, Kiley P. The impact of O(2) on the Fe-S cluster biogenesis requirements of Escherichia coli FNR. J Mol Biol. 2008;384:798-811 pubmed publisher
    ..Taken together, these findings indicate a major role for the Isc pathway in FNR Fe-S cluster biogenesis under both aerobic and anaerobic conditions. ..
  17. Conlan A, Axelrod H, Cohen A, Abresch E, Zuris J, Yee D, et al. Crystal structure of Miner1: The redox-active 2Fe-2S protein causative in Wolfram Syndrome 2. J Mol Biol. 2009;392:143-53 pubmed publisher
    ..The structural and biophysical results are discussed in relation to possible roles of Miner1 in cellular Fe-S management and redox reactions. ..
  18. Veatch J, McMurray M, Nelson Z, Gottschling D. Mitochondrial dysfunction leads to nuclear genome instability via an iron-sulfur cluster defect. Cell. 2009;137:1247-58 pubmed publisher
    ..For a video summary of this article, see the PaperFlick file available with the online Supplemental Data. ..
  19. Stehling O, Netz D, Niggemeyer B, Rösser R, Eisenstein R, Puccio H, et al. Human Nbp35 is essential for both cytosolic iron-sulfur protein assembly and iron homeostasis. Mol Cell Biol. 2008;28:5517-28 pubmed publisher
  20. Cieluch E, Pietryga K, Sarewicz M, Osyczka A. Visualizing changes in electron distribution in coupled chains of cytochrome bc(1) by modifying barrier for electron transfer between the FeS cluster and heme c(1). Biochim Biophys Acta. 2010;1797:296-303 pubmed publisher
  21. Bak D, Zuris J, Paddock M, Jennings P, Elliott S. Redox characterization of the FeS protein MitoNEET and impact of thiazolidinedione drug binding. Biochemistry. 2009;48:10193-5 pubmed publisher
    ..In contrast, a His87Cys mutant negates the ability of TZDs to affect the midpoint potential, suggesting a model of drug binding in which His87 is critical to communication with the FeS center of mitoNEET. ..
  22. Li H, Mapolelo D, Dingra N, Naik S, Lees N, Hoffman B, et al. The yeast iron regulatory proteins Grx3/4 and Fra2 form heterodimeric complexes containing a [2Fe-2S] cluster with cysteinyl and histidyl ligation. Biochemistry. 2009;48:9569-81 pubmed publisher
    ..Overall, these results suggest that the ability of the Fra2-Grx3/4 complex to assemble a [2Fe-2S] cluster may act as a signal to control the iron regulon in response to cellular iron status in yeast. ..
  23. Marinoni I, Nonnis S, Monteferrante C, Heathcote P, H rtig E, B ttger L, et al. Characterization of L-aspartate oxidase and quinolinate synthase from Bacillus subtilis. FEBS J. 2008;275:5090-107 pubmed publisher
    ..Moreover, for the first time, it was shown that the interaction between NadA and NadB is not species-specific between B. subtilis and Escherichia coli...
  24. Mochel F, Knight M, Tong W, Hernandez D, Ayyad K, Taivassalo T, et al. Splice mutation in the iron-sulfur cluster scaffold protein ISCU causes myopathy with exercise intolerance. Am J Hum Genet. 2008;82:652-60 pubmed publisher
    ..ISCU interacts with the Friedreich ataxia gene product frataxin in iron-sulfur cluster biosynthesis. Our results therefore extend the range of known human diseases that are caused by defects in iron-sulfur cluster biogenesis...
  25. Olsson A, Lind L, Thornell L, Holmberg M. Myopathy with lactic acidosis is linked to chromosome 12q23.3-24.11 and caused by an intron mutation in the ISCU gene resulting in a splicing defect. Hum Mol Genet. 2008;17:1666-72 pubmed publisher
    ..To conclude, our data strongly suggest that an intron mutation in the ISCU gene, leading to incorrectly spliced mRNA, is the cause of myopathy with lactic acidosis in this family. ..
  26. Kim J, Füzéry A, Tonelli M, Ta D, Westler W, Vickery L, et al. Structure and dynamics of the iron-sulfur cluster assembly scaffold protein IscU and its interaction with the cochaperone HscB. Biochemistry. 2009;48:6062-71 pubmed publisher
    ..We conclude that the IscU-HscB complex exists as two (or more) distinct states that interconvert at a rate much faster than the rate of dissociation of the complex and that HscB binds to and stabilizes the ordered state of apo-IscU. ..
  27. Fontecave M, Ollagnier de Choudens S. Iron-sulfur cluster biosynthesis in bacteria: Mechanisms of cluster assembly and transfer. Arch Biochem Biophys. 2008;474:226-37 pubmed publisher
  28. Li H, Gakh O, Smith D, Isaya G. Oligomeric yeast frataxin drives assembly of core machinery for mitochondrial iron-sulfur cluster synthesis. J Biol Chem. 2009;284:21971-80 pubmed publisher
    ..These findings suggest that iron-dependent oligomerization is a mechanism by which the iron donor promotes assembly of the core machinery for mitochondrial ISC synthesis. ..
  29. Chatterjee A, Li Y, Zhang Y, Grove T, Lee M, Krebs C, et al. Reconstitution of ThiC in thiamine pyrimidine biosynthesis expands the radical SAM superfamily. Nat Chem Biol. 2008;4:758-65 pubmed publisher
    ..Structural comparisons reveal that HMP-P synthase is homologous to a group of adenosylcobalamin radical enzymes. This similarity supports an evolutionary relationship between these two superfamilies. ..
  30. Kollberg G, Tulinius M, Melberg A, Darin N, Andersen O, Holmgren D, et al. Clinical manifestation and a new ISCU mutation in iron-sulphur cluster deficiency myopathy. Brain. 2009;132:2170-9 pubmed publisher
    ..There was only a slight reduction of mitochondrial IscU in the compound heterozygotes, despite their severe phenotype, indicating that the IscU expressed in these patients is non-functional...
  31. Rottenberg H, Covian R, Trumpower B. Membrane potential greatly enhances superoxide generation by the cytochrome bc1 complex reconstituted into phospholipid vesicles. J Biol Chem. 2009;284:19203-10 pubmed publisher
  32. Nicolet Y, Rubach J, Posewitz M, Amara P, Mathevon C, Atta M, et al. X-ray structure of the [FeFe]-hydrogenase maturase HydE from Thermotoga maritima. J Biol Chem. 2008;283:18861-72 pubmed publisher
    ..Although the overall triose-phosphate isomerase-barrel structure of HydE is very similar to that of biotin synthase, the residues that line the internal cavity are significantly different in the two enzymes...
  33. Bych K, Kerscher S, Netz D, Pierik A, Zwicker K, Huynen M, et al. The iron-sulphur protein Ind1 is required for effective complex I assembly. EMBO J. 2008;27:1736-46 pubmed publisher
    ..Our data suggest that Ind1 facilitates the assembly of Fe-S cofactors and subunits of complex I...
  34. Lin J, Zhou T, Ye K, Wang J. Crystal structure of human mitoNEET reveals distinct groups of iron sulfur proteins. Proc Natl Acad Sci U S A. 2007;104:14640-5 pubmed
    ..UV-visible absorption spectra indicated that mitoNEET can exist in oxidized and reduced states. Our study suggests an electron transfer function for mitoNEET and for other proteins containing the CCCH motif. ..
  35. Hou X, Liu R, Ross S, Smart E, Zhu H, Gong W. Crystallographic studies of human MitoNEET. J Biol Chem. 2007;282:33242-6 pubmed
    ..It is proposed that mitoNEET dimer may interact with other proteins via the surface residues in close proximity to the [2Fe-2S] cluster. ..
  36. Meyer J. Iron-sulfur protein folds, iron-sulfur chemistry, and evolution. J Biol Inorg Chem. 2008;13:157-70 pubmed
    ..Altogether, the data collected and analyzed here suggest that the extant structural landscape of Fe-S proteins has been shaped to a large extent by primeval geochemical conditions on one hand, and iron-sulfur chemistry on the other. ..
  37. Pugh R, Honda M, Leesley H, Thomas A, Lin Y, Nilges M, et al. The iron-containing domain is essential in Rad3 helicases for coupling of ATP hydrolysis to DNA translocation and for targeting the helicase to the single-stranded DNA-double-stranded DNA junction. J Biol Chem. 2008;283:1732-43 pubmed
    ..Although it interacts specifically with the junction, the enzyme binds tightly to ssDNA, and the single-stranded regions of the substrate are the major contributors to the energetics of FacRad3-substrate interactions. ..
  38. Gelling C, Dawes I, Richhardt N, Lill R, Muhlenhoff U. Mitochondrial Iba57p is required for Fe/S cluster formation on aconitase and activation of radical SAM enzymes. Mol Cell Biol. 2008;28:1851-61 pubmed
    ..In keeping with this idea, the human IBA57 homolog C1orf69 complements the iba57Delta growth defects, demonstrating its conserved function throughout the eukaryotic kingdom. ..
  39. Stehling O, Smith P, Biederbick A, Balk J, Lill R, Muhlenhoff U. Investigation of iron-sulfur protein maturation in eukaryotes. Methods Mol Biol. 2007;372:325-42 pubmed publisher
    ..These approaches are crucial to elucidate the mechanisms underlying the maturation of Fe-S proteins and may aid in the identification of new members of this evolutionary ancient process. ..
  40. Bandyopadhyay S, Gama F, Molina Navarro M, Gualberto J, Claxton R, Naik S, et al. Chloroplast monothiol glutaredoxins as scaffold proteins for the assembly and delivery of [2Fe-2S] clusters. EMBO J. 2008;27:1122-33 pubmed publisher
    ..Alternatively, they may function in the storage and/or delivery of preformed Fe-S clusters or in the regulation of the chloroplastic Fe-S cluster assembly machinery. ..
  41. Godman J, Balk J. Genome analysis of Chlamydomonas reinhardtii reveals the existence of multiple, compartmentalized iron-sulfur protein assembly machineries of different evolutionary origins. Genetics. 2008;179:59-68 pubmed publisher
    ..As a haploid, unicellular organism with available forward and reverse genetic tools, Chlamydomonas provides an excellent model system to study Fe-S cluster assembly and its regulation in photosynthetic eukaryotes. ..
  42. Zhang Y, Lyver E, Nakamaru Ogiso E, Yoon H, Amutha B, Lee D, et al. Dre2, a conserved eukaryotic Fe/S cluster protein, functions in cytosolic Fe/S protein biogenesis. Mol Cell Biol. 2008;28:5569-82 pubmed publisher
  43. Pop S, Gupta N, Raza A, Ragsdale S. Transcriptional activation of dehalorespiration. Identification of redox-active cysteines regulating dimerization and DNA binding. J Biol Chem. 2006;281:26382-90 pubmed
    ..Therefore, reversible redox inactivation is manifested at the level of DNA binding. Our studies reveal a strategy for limiting expression of a redox-sensitive pathway by using a thiol-based redox switch in the transcription factor...
  44. Loiseau L, Gerez C, Bekker M, Ollagnier de Choudens S, Py B, Sanakis Y, et al. ErpA, an iron sulfur (Fe S) protein of the A-type essential for respiratory metabolism in Escherichia coli. Proc Natl Acad Sci U S A. 2007;104:13626-31 pubmed
    ..coli. Surprisingly, the erpA gene maps at a distance from any other Fe-S biogenesis-related gene. ErpA is an A-type Fe-S protein that is characterized by an essential role in cellular metabolism. ..
  45. Vickery L, Cupp Vickery J. Molecular chaperones HscA/Ssq1 and HscB/Jac1 and their roles in iron-sulfur protein maturation. Crit Rev Biochem Mol Biol. 2007;42:95-111 pubmed
    ..Additional genetic and biochemical studies are needed to extend these findings to mtHsp70 activities in higher eukaryotes. ..
  46. Hernandez H, Pierrel F, Elleingand E, Garcia Serres R, Huynh B, Johnson M, et al. MiaB, a bifunctional radical-S-adenosylmethionine enzyme involved in the thiolation and methylation of tRNA, contains two essential [4Fe-4S] clusters. Biochemistry. 2007;46:5140-7 pubmed
  47. Ding H, Yang J, Coleman L, Yeung S. Distinct iron binding property of two putative iron donors for the iron-sulfur cluster assembly: IscA and the bacterial frataxin ortholog CyaY under physiological and oxidative stress conditions. J Biol Chem. 2007;282:7997-8004 pubmed
  48. Murphy J, Saltikov C. The cymA gene, encoding a tetraheme c-type cytochrome, is required for arsenate respiration in Shewanella species. J Bacteriol. 2007;189:2283-90 pubmed
  49. Tong W, Rouault T. Metabolic regulation of citrate and iron by aconitases: role of iron-sulfur cluster biogenesis. Biometals. 2007;20:549-64 pubmed
    ..This review discusses the central role of aconitases in intermediary metabolism and explores how iron homeostasis and Fe-S cluster biogenesis regulate the Fe-S cluster switch and modulate intracellular citrate flux. ..
  50. Korbas M, Vogt S, Meyer Klaucke W, Bill E, Lyon E, Thauer R, et al. The iron-sulfur cluster-free hydrogenase (Hmd) is a metalloenzyme with a novel iron binding motif. J Biol Chem. 2006;281:30804-13 pubmed
  51. Cheng V, Ma E, Zhao Z, Rothery R, Weiner J. The iron-sulfur clusters in Escherichia coli succinate dehydrogenase direct electron flow. J Biol Chem. 2006;281:27662-8 pubmed
    ..We hypothesize that this occurs because the midpoint potentials of the [Fe-S] clusters in the native enzyme are poised such that direction of electron transfer from succinate to ubiquinone is favored. ..
  52. Boyer M, Stapleton J, Kuchenreuther J, Wang C, Swartz J. Cell-free synthesis and maturation of [FeFe] hydrogenases. Biotechnol Bioeng. 2008;99:59-67 pubmed
  53. Zeng J, Geng M, Jiang H, Liu Y, Liu J, Qiu G. The IscA from Acidithiobacillus ferrooxidans is an iron-sulfur protein which assemble the [Fe4S4] cluster with intracellular iron and sulfur. Arch Biochem Biophys. 2007;463:237-44 pubmed
    ..The IscA from A. ferrooxidans may function as a scaffold protein for the pre-assembly of Fe-S cluster and then transfer it to target proteins in A. ferrooxidans. ..