iscU

Summary

Gene Symbol: iscU
Description: iron-sulfur cluster assembly scaffold protein
Alias: ECK2526, JW2513, hsm-5, miaC, nifU, yfhN
Species: Escherichia coli str. K-12 substr. MG1655

Top Publications

  1. Agar J, Krebs C, Frazzon J, Huynh B, Dean D, Johnson M. IscU as a scaffold for iron-sulfur cluster biosynthesis: sequential assembly of [2Fe-2S] and [4Fe-4S] clusters in IscU. Biochemistry. 2000;39:7856-62 pubmed
    ..in both prokaryotic and eukaryotic cells is known to be mediated by two highly conserved proteins, termed IscS and IscU in prokaryotes...
  2. Leipuviene R, Qian Q, Bjork G. Formation of thiolated nucleosides present in tRNA from Salmonella enterica serovar Typhimurium occurs in two principally distinct pathways. J Bacteriol. 2004;186:758-66 pubmed
    ..A mutant (iscU52) was isolated that carried an amino acid substitution (S107T) in the IscU protein, which functions as a major scaffold in the formation of [Fe-S] clusters...
  3. Silberg J, Tapley T, Hoff K, Vickery L. Regulation of the HscA ATPase reaction cycle by the co-chaperone HscB and the iron-sulfur cluster assembly protein IscU. J Biol Chem. 2004;279:53924-31 pubmed
    ..hsp70 molecular chaperone from Escherichia coli, is regulated by the iron-sulfur cluster assembly protein IscU and the J-type co-chaperone HscB...
  4. Johnson D, Dean D, Smith A, Johnson M. Structure, function, and formation of biological iron-sulfur clusters. Annu Rev Biochem. 2005;74:247-81 pubmed
  5. Bonomi F, Iametti S, Ta D, Vickery L. Multiple turnover transfer of [2Fe2S] clusters by the iron-sulfur cluster assembly scaffold proteins IscU and IscA. J Biol Chem. 2005;280:29513-8 pubmed
    b>IscU/Isu and IscA/Isa (and related NifU and SufA proteins) have been proposed to serve as molecular scaffolds for preassembly of [FeS] clusters to be used in the biogenesis of iron-sulfur proteins...
  6. Urbina H, Silberg J, Hoff K, Vickery L. Transfer of sulfur from IscS to IscU during Fe/S cluster assembly. J Biol Chem. 2001;276:44521-6 pubmed publisher
    The cysteine desulfurase enzymes NifS and IscS provide sulfur for the biosynthesis of Fe/S proteins. NifU and IscU have been proposed to serve as template or scaffold proteins in the initial Fe/S cluster assembly events, but the mechanism ..
  7. 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
    b>IscU is a scaffold protein that functions in iron-sulfur cluster assembly and transfer...
  8. Bandyopadhyay S, Chandramouli K, Johnson M. Iron-sulfur cluster biosynthesis. Biochem Soc Trans. 2008;36:1112-9 pubmed publisher
  9. Ayala Castro C, Saini A, Outten F. Fe-S cluster assembly pathways in bacteria. Microbiol Mol Biol Rev. 2008;72:110-25, table of contents pubmed publisher
    ..Here we attempt to summarize recent advances and to highlight new avenues of research in the field of Fe-S cluster assembly. ..

More Information

Publications51

  1. Takahashi Y, Nakamura M. Functional assignment of the ORF2-iscS-iscU-iscA-hscB-hscA-fdx-ORF3 gene cluster involved in the assembly of Fe-S clusters in Escherichia coli. J Biochem. 1999;126:917-26 pubmed
    ..In Escherichia coli, genes in the ORF1-ORF2-iscS-iscU-iscA-hscB-hsc A-fdx-ORF3 cluster (the isc gene cluster) should be involved in the assembly of the Fe-S cluster ..
  2. Smith A, Frazzon J, Dean D, Johnson M. Role of conserved cysteines in mediating sulfur transfer from IscS to IscU. FEBS Lett. 2005;579:5236-40 pubmed
    The role of the three conserved cysteine residues on Azotobacter vinelandii IscU in accepting sulfane sulfur and forming a covalent complex with IscS has been evaluated using electrospray-ionization mass spectrometry studies of variants ..
  3. Cupp Vickery J, Peterson J, Ta D, Vickery L. Crystal structure of the molecular chaperone HscA substrate binding domain complexed with the IscU recognition peptide ELPPVKIHC. J Mol Biol. 2004;342:1265-78 pubmed
    ..a specialized bacterial Hsp70-class molecular chaperone, interacts with the iron-sulfur cluster assembly protein IscU by recognizing a conserved LPPVK sequence motif...
  4. Ramelot T, Cort J, Goldsmith Fischman S, Kornhaber G, Xiao R, Shastry R, et al. Solution NMR structure of the iron-sulfur cluster assembly protein U (IscU) with zinc bound at the active site. J Mol Biol. 2004;344:567-83 pubmed
    b>IscU is a highly conserved protein that serves as the scaffold for IscS-mediated assembly of iron-sulfur ([Fe-S]) clusters...
  5. Tokumoto U, Nomura S, Minami Y, Mihara H, Kato S, Kurihara T, et al. Network of protein-protein interactions among iron-sulfur cluster assembly proteins in Escherichia coli. J Biochem. 2002;131:713-9 pubmed
    ..the previous in vitro binding and kinetic experiments, interactions were observed for the combinations of IscS and IscU, IscU and HscB, IscU and HscA, and HscB and HscA...
  6. Layer G, Ollagnier de Choudens S, Sanakis Y, Fontecave M. Iron-sulfur cluster biosynthesis: characterization of Escherichia coli CYaY as an iron donor for the assembly of [2Fe-2S] clusters in the scaffold IscU. J Biol Chem. 2006;281:16256-63 pubmed
    ..demonstrated to be functional in vitro as an iron donor during [Fe-S] cluster assembly on the scaffold protein IscU in the presence of IscS and cysteine...
  7. Hoff K, Cupp Vickery J, Vickery L. Contributions of the LPPVK motif of the iron-sulfur template protein IscU to interactions with the Hsc66-Hsc20 chaperone system. J Biol Chem. 2003;278:37582-9 pubmed publisher
    ..A charge mutant containing the motif sequence of NifU, IscU(V102E), did not bind the ATP or ADP states of Hsc66 but did bind Hsc20 and weakly stimulated Hsc66 ATPase in ..
  8. Kato S, Mihara H, Kurihara T, Takahashi Y, Tokumoto U, Yoshimura T, et al. Cys-328 of IscS and Cys-63 of IscU are the sites of disulfide bridge formation in a covalently bound IscS/IscU complex: implications for the mechanism of iron-sulfur cluster assembly. Proc Natl Acad Sci U S A. 2002;99:5948-52 pubmed publisher
    IscS and IscU from Escherichia coli cooperate with each other in the biosynthesis of iron-sulfur clusters. IscS catalyzes the desulfurization of L-cysteine to produce L-alanine and sulfur...
  9. Zheng L, Cash V, Flint D, Dean D. Assembly of iron-sulfur clusters. Identification of an iscSUA-hscBA-fdx gene cluster from Azotobacter vinelandii. J Biol Chem. 1998;273:13264-72 pubmed
    ..vinelandii previously designated orf6. These genes have been designated iscU and iscA, respectively...
  10. Nuth M, Yoon T, Cowan J. Iron-sulfur cluster biosynthesis: characterization of iron nucleation sites for assembly of the [2Fe-2S]2+ cluster core in IscU proteins. J Am Chem Soc. 2002;124:8774-5 pubmed
    ISU (eukaryotes) and IscU (prokaryotes) are a homologous family of proteins that appear to provide a platform for assembly of [2Fe-2S] centers prior to delivery to a target apoprotein...
  11. Hoff K, Silberg J, Vickery L. Interaction of the iron-sulfur cluster assembly protein IscU with the Hsc66/Hsc20 molecular chaperone system of Escherichia coli. Proc Natl Acad Sci U S A. 2000;97:7790-5 pubmed
    The iscU gene in bacteria is located in a gene cluster encoding proteins implicated in iron-sulfur cluster assembly and an hsc70-type (heat shock cognate) molecular chaperone system, iscSUA-hscBA...
  12. Kurihara T, Mihara H, Kato S, Yoshimura T, Esaki N. Assembly of iron-sulfur clusters mediated by cysteine desulfurases, IscS, CsdB and CSD, from Escherichia coli. Biochim Biophys Acta. 2003;1647:303-9 pubmed
    ..We found that each of them facilitates the formation of the iron-sulfur cluster of ferredoxin in vitro. Since IscU, an iron-sulfur protein of E...
  13. Silberg J, Hoff K, Tapley T, Vickery L. The Fe/S assembly protein IscU behaves as a substrate for the molecular chaperone Hsc66 from Escherichia coli. J Biol Chem. 2001;276:1696-700 pubmed
    b>IscU, a NifU-like Fe/S-escort protein, binds to and stimulates the ATPase activity of Hsc66, a hsp70-type molecular chaperone. We present evidence that stimulation arises from interactions of IscU with the substrate-binding site of Hsc66...
  14. Iannuzzi C, Adinolfi S, Howes B, Garcia Serres R, Clémancey M, Latour J, et al. The role of CyaY in iron sulfur cluster assembly on the E. coli IscU scaffold protein. PLoS ONE. 2011;6:e21992 pubmed publisher
    ..of cluster formation of CyaY, the bacterial ortholog of frataxin, on cluster formation on the scaffold protein IscU. Frataxin/CyaY is a highly conserved protein implicated in an incurable ataxia in humans...
  15. Djaman O, Outten F, Imlay J. Repair of oxidized iron-sulfur clusters in Escherichia coli. J Biol Chem. 2004;279:44590-9 pubmed
  16. Nakamura M, Saeki K, Takahashi Y. Hyperproduction of recombinant ferredoxins in escherichia coli by coexpression of the ORF1-ORF2-iscS-iscU-iscA-hscB-hs cA-fdx-ORF3 gene cluster. J Biochem. 1999;126:10-8 pubmed
    ..We examined the coexpression of the E. coli ORF1-ORF2-iscS-iscU-iscA-hscB-hsc A-fdx-ORF3 gene cluster, which has recently been suggested to be involved in the formation or repair ..
  17. Bonomi F, Iametti S, Morleo A, Ta D, Vickery L. Studies on the mechanism of catalysis of iron-sulfur cluster transfer from IscU[2Fe2S] by HscA/HscB chaperones. Biochemistry. 2008;47:12795-801 pubmed publisher
    ..The HscA/HscB chaperone/cochaperone system accelerates transfer of iron-sulfur clusters from the FeS-scaffold protein IscU (IscU(2)[2Fe2S], holo-IscU) to acceptor proteins in an ATP-dependent manner...
  18. Ding H, Clark R. Characterization of iron binding in IscA, an ancient iron-sulphur cluster assembly protein. Biochem J. 2004;379:433-40 pubmed
    Iron-sulphur clusters are one of the most common types of redox centre in biology. At least six proteins (IscS, IscU, IscA, HscB, HscA and ferredoxin) have been identified as being essential for the biogenesis of iron-sulphur proteins in ..
  19. Yoon H, Knight S, Pandey A, Pain J, Turkarslan S, Pain D, et al. Turning Saccharomyces cerevisiae into a Frataxin-Independent Organism. PLoS Genet. 2015;11:e1005135 pubmed publisher
    ..Direct targeting of the entire E. coli IscU to ∆yfh1 mitochondria also ameliorated the mutant phenotypes...
  20. Füzéry A, Tonelli M, Ta D, Cornilescu G, Vickery L, Markley J. Solution structure of the iron-sulfur cluster cochaperone HscB and its binding surface for the iron-sulfur assembly scaffold protein IscU. Biochemistry. 2008;47:9394-404 pubmed publisher
    The interaction between IscU and HscB is critical for successful assembly of iron-sulfur clusters. NMR experiments were performed on HscB to investigate which of its residues might be part of the IscU binding surface...
  21. Riber L, Olsson J, Jensen R, Skovgaard O, Dasgupta S, Marinus M, et al. Hda-mediated inactivation of the DnaA protein and dnaA gene autoregulation act in concert to ensure homeostatic maintenance of the Escherichia coli chromosome. Genes Dev. 2006;20:2121-34 pubmed
    ..Based on these observations, we propose that both RIDA and dnaA gene autoregulation are required as homeostatic mechanisms to ensure that initiation of replication occurs at the same time relative to cell mass in each cell cycle. ..
  22. Yang J, Bitoun J, Ding H. Interplay of IscA and IscU in biogenesis of iron-sulfur clusters. J Biol Chem. 2006;281:27956-63 pubmed
    ..The gene that encodes IscS is a member of an operon iscSUA, which also encodes two highly conserved proteins: IscU and IscA...
  23. Hoff K, Ta D, Tapley T, Silberg J, Vickery L. Hsc66 substrate specificity is directed toward a discrete region of the iron-sulfur cluster template protein IscU. J Biol Chem. 2002;277:27353-9 pubmed publisher
    ..Only a single substrate, the Fe/S template protein IscU, has been identified for the Hsc66/Hsc20 system, but the mechanism by which Hsc66 selectively binds IscU is unknown...
  24. Roche B, Agrebi R, Huguenot A, Ollagnier de Choudens S, Barras F, Py B. Turning Escherichia coli into a Frataxin-Dependent Organism. PLoS Genet. 2015;11:e1005134 pubmed publisher
    ..Here, we have demonstrated that a single mutation in the scaffold protein IscU rendered E. coli viability strictly dependent upon a functional CyaY...
  25. Adrover M, Howes B, Iannuzzi C, Smulevich G, Pastore A. Anatomy of an iron-sulfur cluster scaffold protein: Understanding the determinants of [2Fe-2S] cluster stability on IscU. Biochim Biophys Acta. 2015;1853:1448-56 pubmed publisher
    ..Here, we have addressed this question by studying the determinants of the 2Fe-2S cluster stability in the IscU/Isu protein scaffold...
  26. Adinolfi S, Rizzo F, Masino L, Nair M, Martin S, Pastore A, et al. Bacterial IscU is a well folded and functional single domain protein. Eur J Biochem. 2004;271:2093-100 pubmed
    ..Of the two main proteins involved in cluster formation, NifS/IscS and NifU/IscU, only the former has been well studied from a structural point of view...
  27. Ding H, Clark R, Ding B. IscA mediates iron delivery for assembly of iron-sulfur clusters in IscU under the limited accessible free iron conditions. J Biol Chem. 2004;279:37499-504 pubmed
    ..suggests that IscS, a cysteine desulfurase, provides sulfur for assembly of transient iron-sulfur clusters in IscU. IscU appears to act as a scaffold and eventually transfers the assembled clusters to target proteins...
  28. Wu G, Li L. Biochemical characterization of iron-sulfur cluster assembly in the scaffold IscU of Escherichia coli. Biochemistry (Mosc). 2012;77:135-42 pubmed publisher
    ..Although iron or sulfur binds with IscU equivalently, 2-fold amount of iron or cysteine compared with that of IscU is better for the cluster formation, ..
  29. Ding B, Smith E, Ding H. Mobilization of the iron centre in IscA for the iron-sulphur cluster assembly in IscU. Biochem J. 2005;389:797-802 pubmed
    ..is an iron-binding protein that can provide iron for the iron-sulphur cluster assembly in a proposed scaffold IscU. To determine how the iron centre in IscA is transferred for the iron-sulphur cluster assembly in IscU, we explore ..
  30. Tapley T, Vickery L. Preferential substrate binding orientation by the molecular chaperone HscA. J Biol Chem. 2004;279:28435-42 pubmed
    HscA, a specialized bacterial hsp70-class chaperone, interacts with the iron-sulfur cluster assembly protein IscU by recognizing a conserved LPPVK sequence motif at positions 99-103...
  31. Schwartz C, Giel J, Patschkowski T, Luther C, Ruzicka F, Beinert H, et al. IscR, an Fe-S cluster-containing transcription factor, represses expression of Escherichia coli genes encoding Fe-S cluster assembly proteins. Proc Natl Acad Sci U S A. 2001;98:14895-900 pubmed publisher
    ..an ORF located immediately upstream of genes coding for the Escherichia coli Fe-S cluster assembly proteins, IscS, IscU, and IscA...
  32. Kim J, Bothe J, Frederick R, Holder J, Markley J. Role of IscX in iron-sulfur cluster biogenesis in Escherichia coli. J Am Chem Soc. 2014;136:7933-42 pubmed publisher
    ..binds iron ions and interacts with the cysteine desulfurase (IscS) and the scaffold protein for cluster assembly (IscU), and it has been proposed that IscX functions either as an iron supplier or a regulator of Fe-S cluster biogenesis...
  33. Ding H, Harrison K, Lu J. Thioredoxin reductase system mediates iron binding in IscA and iron delivery for the iron-sulfur cluster assembly in IscU. J Biol Chem. 2005;280:30432-7 pubmed
    ..IscA is an iron-binding protein that can provide iron for the iron-sulfur cluster assembly in a proposed scaffold IscU (Ding H., Clark, R. J., and Ding, B. (2004) J. Biol. Chem. 279, 37499-37504)...
  34. Markley J, Kim J, Dai Z, Bothe J, Cai K, Frederick R, et al. Metamorphic protein IscU alternates conformations in the course of its role as the scaffold protein for iron-sulfur cluster biosynthesis and delivery. FEBS Lett. 2013;587:1172-9 pubmed publisher
    b>IscU from Escherichia coli, the scaffold protein for iron-sulfur cluster biosynthesis and delivery, populates a complex energy landscape...
  35. Smith A, Agar J, Johnson K, Frazzon J, Amster I, Dean D, et al. Sulfur transfer from IscS to IscU: the first step in iron-sulfur cluster biosynthesis. J Am Chem Soc. 2001;123:11103-4 pubmed
  36. Tokumoto U, Kitamura S, Fukuyama K, Takahashi Y. Interchangeability and distinct properties of bacterial Fe-S cluster assembly systems: functional replacement of the isc and suf operons in Escherichia coli with the nifSU-like operon from Helicobacter pylori. J Biochem. 2004;136:199-209 pubmed
    ..While the differences between ISC and SUF were small with respect to the complementing activity, the SUF system appears to be more advantageous for bacterial growth in the presence of hydrogen peroxide. ..
  37. Tokumoto U, Takahashi Y. Genetic analysis of the isc operon in Escherichia coli involved in the biogenesis of cellular iron-sulfur proteins. J Biochem. 2001;130:63-71 pubmed
    ..Strains with mutations in the iscU, hscB, hscA, and fdx genes also exhibited conspicuous phenotypical consequences almost identical to one another...
  38. Shi R, Proteau A, Villarroya M, Moukadiri I, Zhang L, Trempe J, et al. Structural basis for Fe-S cluster assembly and tRNA thiolation mediated by IscS protein-protein interactions. PLoS Biol. 2010;8:e1000354 pubmed publisher
    ..Several IscS-interacting partners including IscU, a scaffold for Fe-S cluster assembly; TusA, the first member of a sulfur relay leading to sulfur incorporation ..
  39. Frazzon J, Fick J, Dean D. Biosynthesis of iron-sulphur clusters is a complex and highly conserved process. Biochem Soc Trans. 2002;30:680-5 pubmed
    ..enzyme (NifS) that is involved in the activation of sulphur from l-cysteine, and a molecular scaffold protein (NifU) upon which [Fe-S] cluster precursors are formed...
  40. Fontecave M, Choudens S, Py B, Barras F. Mechanisms of iron-sulfur cluster assembly: the SUF machinery. J Biol Inorg Chem. 2005;10:713-21 pubmed
  41. Ollagnier de Choudens S, Sanakis Y, Fontecave M. SufA/IscA: reactivity studies of a class of scaffold proteins involved in [Fe-S] cluster assembly. J Biol Inorg Chem. 2004;9:828-38 pubmed
    ..No cluster transfer from IscA to IscU, another scaffold of the isc operon, could be observed, whereas IscU was shown to be an efficient cluster source ..
  42. Ranquet C, Ollagnier de Choudens S, Loiseau L, Barras F, Fontecave M. Cobalt stress in Escherichia coli. The effect on the iron-sulfur proteins. J Biol Chem. 2007;282:30442-51 pubmed
    ..In contrast, it reacts with labile ones present in scaffold proteins (IscU, SufA) involved in iron-sulfur cluster biosynthesis...