Abstract
The Ferric uptake regulator (Fur) protein is a global iron regulator found in most prokaryotes. Although the Fur protein is involved in a variety of metabolic pathways, it is specifically known for the regulation of several iron responsive genes. It binds to the highly conserved sequences located in the upstream promoter region known as iron boxes, using ferrous ion as a co-repressor. Apart from that, the Fur protein is also directly/indirectly involved in a variety of other crucial physiological pathways. Hence, understanding the mechanism of action and the mechanistic pathways of iron regulation by Fur is necessary and important. The basic understanding of the functioning and properties of Fur protein along with its role, interaction and regulation at various levels in cyanobacteria has been discussed in detail.
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References
Abed RMM, Garcia-Pichel F (2001) Long-term compositional changes after transplant in a microbial mat cyanobacterial community revealed using a polyphasic approach. Environ Microbiol 3:53–62
Ahn BE, Cha J, Lee EJ, Han AR, Thompson CJ, Roe JH (2006) Nur, a nickel-responsive regulator of the Fur family, regulates superoxide dismutases and nickel transport in Streptomyces coelicolor. Mol Microbiol 59:1848–1858
Althaus EW, Outten CE, Olson KE, Cao H, O’Halloran TV (1999) The ferric uptake regulation (Fur) repressor is a zinc metalloprotein. Biochemistry 38:6559–6569
Andrews SC, Robinson AK, Rodriguez-Quinones F (2003) Bacterial iron homeostasis. FEMS Microbiol Rev 27:215–237
Archibald F (1983) Lactobacillus plantarum, an organism not requiring iron. FEMS Microbiol Lett 19:29–32
Bagg A, Neilands JB (1987) Ferric uptake regulation protein acts as a repressor, employing iron (II) as a cofactor to bind the operator of an iron transport operon in Escherichia coli. Biochemistry 26:5471–5477
Baichoo N, Helmann JD (2002) Recognition of DNA by Fur: a reinterpretation of the Fur box consensus sequence. J Bacteriol 184:5826–5832
Baichoo N, Wang T, Ye R, Helmann JD (2002) Global analysis of the Bacillus subtilis Fur regulon and the iron starvation stimulon. Mol Microbiol 45:1613–1629
Bailey TL, Elkan C (1994) Fitting a mixture model by expectation maximization to discover motifs in biopolymers. In: Second International Conference on Intelligent Systems for Molecular Biology. AAAI Press, Menlo Park, pp 28–36
Barnett JP, Millard A, Ksibe AZ, Scanlan DJ, Schmid R, Blindauer CA (2012) Mining genomes of marine cyanobacteria for elements of zinc homeostasis. Front Microbiol 3:1–21
Barton HA, Johnson Z, Cox CD, Vasil AI, Vasil ML (1996) Ferric uptake regulator mutants of Pseudomonas aeruginosa with distinct alterations in the iron-dependent repression of exotoxin A and siderophores in aerobic and microaerobic environments. Mol Microbiol 21:1001–1017
Bereswill S, Greiner S, van Vliet AH, Waidner B, Fassbinder F, Schiltz E, Kusters JG, Kist M (2000) Regulation of ferritin-mediated cytoplasmic iron storage by the ferric uptake regulator homolog (Fur) of Helicobacter pylori. J Bacteriol 182(21):5948–5953
Bes MT, Hernandez JA, Peleato M, Fillat MF (2001) Cloning, overexpression and interaction of recombinant Fur from the cyanobacterium Anabaena PCC 7119 with isiB and its own promoter. FEMS Microbiol Lett 194:187–192
Boehm M, Yu J, Krynicka V, Barker M, Tichy M, Komenda J (2012) Subunit organization of a Synechocystis hetero-oligomeric thylakoid FtsH complex involved in Photosystem II repair. Plant Cell 24:3669–3683
Botello-Morte L, Gonzalez A, Bes MT, Peleato ML, Fillat MF (2013) Functional genomics of metalloregulators in cyanobacteria. In: Chauvat F, Cassier-Chauvat C (eds) Genomics of Cyanobacteria. Academic, New York, pp 107–156
Botello-Morte L, Bes TM, Heras B, Fernandez-Otal A, Peleato ML, Fillat MF (2014) Unraveling the redox properties of the global regulator FurA from Anabaena sp. PCC 7120: Disulfide reductase activity based on its CXXC Motifs. Antiox Redox Signal 20:1396–1406
Boyd PW, Watson AJ, Law CS, Abraham ER, Trull T, Murdoch R, Bakker DCE, Bowie AR, Buesseler KO, Chang H, Charette M, Croot P, Downing K, Frew R, Gall M, Hadfield M, Hall J, Harvey M, Jameson G, LaRoche J, Liddicoat M, Ling R, Maldonado MT, McKay RM, Nodder S, Pickmere S, Pridmore R, Rintoul S, Safi K, Sutton P, Strzepek R, Tanneberger K, Turner S, Waite A, Zeldis J (2000) A mesoscale phytoplankton bloom in the polar Southern Ocean stimulated by iron fertilization. Nature 407:695–702
Brahamsha B, Haselkorn R (1992) Identification of multiple RNA polymerase sigma factor homologs in the cyanobacterium Anabaena sp. strain PCC 7120: cloning, expression, and inactivation of the sigB and sigC genes. J Bacteriol 174:7273–7282
Braun V, Hantke K (1991) Genetics of bacterial iron transport. In: Winkelmann G (ed) CRC handbook of microbial iron chelates. CRC Press, Boca Raton, pp 107–138
Browning DF, Busby SJ (2004) The regulation of bacterial transcription initiation. Nat Rev Microbiol 2:57–65
Bsat N, Helmann JD (1999) Interaction of Bacillus subtilis Fur (ferric uptake repressor) with the dhb operator in vitro and in vivo. J Bacteriol 181:4299–4307
Bsat N, Herbig A, Casillas-Martinez L, Setlow P, Helmann JD (1998) Bacillus subtilis contains multiple Fur homologues: identification of the iron uptake (Fur) and peroxide regulon (PerR) repressors. Mol Microbiol 29:189–198
Bullen JJ, Rogers HJ, Griffiths E (1978) Role of iron in bacterial infections. In: Arber W, Henle W, Hofschneider PH, Humphrey JH, Klein J, Koldovský P, Koprowski H, Maaløe O, Melchers F, Rott R, Schweiger HG, Syruek, L, Vogt PK (eds) Curr Top Microbiol Immunol. Springer-Verlag Berlin Heidelberg, Vol 80, pp 1–35
Calderwood S, Mekalanos JJ (1988) Conformation of the Fur operator site by insertion of a synthetic oligonucleotide into an operon fusion plasmid. J Bacteriol 170:1015–1017
Chen Q, Crosa JH (1996) Antisense RNA, Fur, iron, and the regulation of iron transport genes in Vibrio anguillarum. J Biol Chem 271:18885–18891
Christoffersen CA, Brickman TJ, Hook-Barnard I, McIntosh MA (2001) Regulatory architecture of the iron regulated fepD-ybdA bidirectional promoter region in Escherichia coli. J Bacteriol 183:2059–2070
Cornelis P, Wie Q, Andrews SC, Vinckx T (2011) Iron homeostasis and management of oxidative stress response in bacteria. Metallomics 3:540–549
Cox CD (1980) Iron uptake with ferric pyochelin and ferric citrate by Pseudomonas aeruginosa. J Bacteriol 142:581–587
Cox CD, Rinehart KL, Moore ML, Cook JC (1982) Pyochelin: novel structure of an iron chelating growth promoter for Pseudomonas aeruginosa. Proc Natl Acad Sci 78:4256–4260
Coy M (1995) The interaction of the ferric uptake regulation protein with DNA. Biochem Biophys Res Commu 212:784–792
Coy M, Neilands JB (1991) Structural dynamics and functional domains of the Fur protein. Biochemistry 30:8201–8210
Davis BM, Quinones M, Pratt J, Ding Y, Waldor MK (2005) Characterization of the small untranslated RNA RyhB and its regulon in Vibrio cholerae. J Bacteriol 187:4005–4014
de Figueiredo DR, Azeiteiro UM, Esteves SM, Goncalves FJM, Pereira MJ (2004) Microcystin- producing blooms- a serious global public health issue. Exotoxicol Environ Saf 59:151–163
de Lorenzo V, Wee S, Herrero M, Neilands JB (1987) Operator sequences of the aerobactin operon of plasmid ColV-K30 binding the ferric uptake regulation (Fur) repressor. J Bacteriol 169:2624–2630
Delany I, Spohn G, Rappuoli R, Scarlato V (2001) The Fur repressor controls transcription of iron-activated and -repressed genes in Helicobacter pylori. Mol Microbiol 42:1297–1309
Delany I, Spohn G, Pacheco A-B F, Ieva R, Alaimo C, Rappuoli R, Scarlato V (2002) Autoregulation of Helicobacter pylori Fur revealed by functional analysis of the iron-binding site. Mol Microbiol 46(4):1107–1122
Delany I, Rappuoli R, Scarlato V (2004) Fur functions as an activator and as a repressor of putative virulence gene in Neisseria meningitidis. Mol Microbiol 54:1081–1090
Deore SR, Bansal GK (2013) A study on health hazards caused by microcystins to the animal life. Int J Chem Sci Appl 4:24–28
Dubrac S, Touati D (2000) Fur positive regulation of iron superoxide dismutase in Escherichia coli: functional analysis of the sodB promoter. J Bacteriol 182:3802–3808
Ducey TF, Carson MB, Orvis J, Stintzi AP, Dyer DW (2005) Identification of the iron-responsive genes of Neisseria gonorrhoeae by microarray analysis in defined medium. J Bacteriol 187:4865–4874
Duhring U, Axmann IM, Hess WR, Wilde A (2006) An internal antisense RNA regulates expression of the photosynthesis gene isiA. Proc Natl Acad Sci 103:7054–7058
Ernst JF, Bennett RL, Rothfield LI (1978) Constitutive expression of the iron enterochelin and ferrichrome uptake systems in a mutant strain of Salmonella typhimurium. J Bacteriol 135:928–934
Ernst FD, Homuth G, Stoof J, Mader U, Waidner B, Kuipers EJ, Kist M, Kusters JG, Bereswill S, van Vliet AH (2005) Iron-responsive regulation of the Helicobacter pylori iron-cofactored superoxide dismutase SodB is mediated by Fur. J Bacteriol 187(11):3687–3692
Escolar L, de Lorenzo V, Pearez-Martoan J (1997) Metalloregulation in vitro of the aerobactin promoter of Escherichia coli by the Fur (ferric uptake regulation) protein. Mol Microbiol 26:799–808
Escolar L, Perez-Martın J, de Lorenzo V (1998) Binding of the Fur (ferric uptake regulator) repressor of Escherichia coli to arrays of the GATAAT sequence. J Mol Biol 283:537–547
Ferrao-Filho AS, Kozlowsky-Suzuki B (2011) Cyanotoxin: bioaccumulation and effects on aquatic animals. Mar Drug 9:2729–2772
Ferreira F, Straus NA (1994) Iron deprivation in cyanobacteria. J Appl Phycol 6:199–210
Ferris JP (2005) Mineral catalysis and prebiotic synthesis: montmorillonite-catalyzed formation of RNA. Elements 1:145–149
Fillat MF (2014) The FUR (ferric uptake regulator) superfamily: diversity and versatility of key transcriptional regulators. Arch Biochem Biophys 546:41–52
Florencio FJ, Perez-Perez ME, Lopez-Maury L, Mata-Cabana A, Lindahl M (2006) The diversity and complexity of the cyanobacterial thioredoxin systems. Photosynth Res 89:157–171
Fuangthong M, Helmann JD (2003) Recognition of DNA by three ferric uptake regulator (Fur) homologs in Bacillus subtilis. J Bacteriol 185:6348–6357
Gaballa A, Antelmann H, Aguilar C, Khakh SK, Song KB, Smaldone GT, Helmann JD (2008) The Bacillus subtilis iron-sparing response is mediated by a Fur-regulated small RNA and three small, basic proteins. Proc Natl Acad Sci U S A 105:11927–11932
Gao H, Zhou D, Li Y, Guo Z, Han Y, Song Y, Zhai J, Du Z, Wang X, Lu J, Yang R (2008) The iron-responsive Fur regulon in Yersinia pestis. J Bacteriol 190:3063–3075
Ghassemian M, Straus NA (1996) Fur regulates the expression of iron-stress genes in the cyanobacterium Synechococcus sp. strain PCC 7942. Microbiology 142:1469–1476
Gonzalez A, Bes MT, Peleato ML, Fillat MF (2011) Unraveling the regulatory function of FurA in Anabaena sp. PCC 7120 through 2-D DIGE proteomic analysis. J Proteomics 74:660–671
Gonzalez A, Bes MT, Valladares A, Peleato ML, Fillat MF (2012) FurA is the master regulator of iron homeostasis and modulates the expression of tetrapyrrole biosynthesis genes in Anabaena sp. PCC 7120. Environ Microbiol 14:3175–3187
Gonzalez A, Angarica AE, Sancho J, Fillat MF (2014) The FurA regulon in Anabaena sp. PCC 7120: in silico prediction and experimental validation of novel target genes. Nucleic Acids Res 42:4833–4846
Gottesman S (2002) Stealth regulation: biological circuits with small RNA switches. Genes Dev 16:2829–2842
Griggs DW, Konisky J (1989) Mechanism for iron-regulated transcription of the Escherichia coli cir gene: metal-dependent binding of Fur protein to the promoters. J Bacteriol 171:1048–1054
Griggs DG, Tharp BB, Konisky J (1987) Cloning and promoter identification of the iron-regulated cir gene of Escherichia coli. J Bacteriol 169:5343–5352
Hahn JS, Oh SY, Roe JH (2000) Regulation of the furA and catC Operon, encoding a Ferric Uptake Regulator homologue and Catalase-Peroxidase, respectively, in Streptomyces coelicolor A3. J Bacteriol 182:3767–3774
Hall HK, Foster JW (1996) The role of Fur in the acid tolerance response of Salmonella typhimurium is physiologically and genetically separable from its role in iron acquisition. J Bacteriol 178:5683–5691
Hamza I, Chauhan VS, Hassett R, O’ Brian MR (1998) The bacterial Irr protein is required for coordination of heme biosynthesis with iron availability. J Biol Chem 273:21669–22167
Hantke K (1981) Regulation of ferric iron transport in Escherichia coli K12: isolation of a constitutive mutant. Mol Gen Genet 182:288–292
Hayat R, Ali S, Amara U, Khalid R, Ahmed I (2010) Soil beneficial bacteria and their role in plant growth promotion: a review. Ann Microbiol 60:579–598
Heidrich C, Hantke K, Bierbaum G, Sahl HG (1996) Identification and analysis of a gene encoding a Fur-like protein of Staphylococcus epidermidis. FEMS Microbiol Lett 14:253–259
Hennecke H (1990) Regulation of bacterial gene expression by metal- protein complexes. Mol Microbiol 4:1621–1628
Heras B, Kurz M, Shouldice SR, Martin JL (2007) The name’s bond…disulfide bond. Curr Opin Struct Biol 17:691–698
Hernandez JA, Bes MT, Fillat MF, Neira JL, Peleato ML (2002) Biochemical analysis of the recombinant Fur (ferric uptake regulator) protein from Anabaena PCC 7119: factors affecting its oligomerization state. Biochem J 366:315–322
Hernandez JA, Lopez-Gomollon S, Bes MT, Fillat MF, Peleato ML (2004a) Three Fur homologues from Anabaena sp. PCC 7120: exploring reciprocal protein-promoter recognition. FEMS Microbiol Lett 236:275–282
Hernandez JA, Peleato ML, Fillat MF, Bes MT (2004b) Heme binds to and inhibits the DNA-binding activity of the global regulator FurA from Anabaena sp. PCC 7120. FEBS Lett 577:35–41
Hernandez JA, Meier J, Barrera FN, de los Panos OR, Hurtado-Gomez E, Bes MT, Fillat MF, Peleato ML, Cavasotto CN, Neira JL (2005) The conformational stability and thermodyanamics of FurA (Ferric Uptake Regulator) from Anabaena sp. PCC 7119. Biophys J 89:4188–4200
Hernandez JA, Muro-Pastor AM, Flores E, Bes MT, Peleato ML, Fillat MF (2006a) Identification of a furA cis antisense RNA in the cyanobacterium Anabaena sp. PCC 7120. J Mol Biol 355:325–334
Hernandez JA, Lopez-Gomollon S, Muro-Pastor A, Valladares A, Bes MT, Peleato ML, Fillat MF (2006b) Interaction of FurA from Anabaena sp. PCC 7120 with DNA: A reducing environment and the presence of Mn2+ are positive effectors in the binding to isiB and furA promoters. BioMethods 19:259–268
Hernandez JA, Pellicer S, Huang L, Peleato ML, Fillat MF (2007) FurA modulates gene expression of alr3808, a DpsA homologue in Nostoc (Anabaena) sp. PCC 7120. FEBS Lett 581:1351–1356
Hernandez JA, Alonso I, Pellicer S, Luisa Peleato M, Cases R, Strasser RJ, Barja F, Fillat MF (2010) Mutants of Anabaena sp. PCC 7120 lacking alr1690 and α-furA antisense RNA show a pleiotropic phenotype and altered photosynthetic machinery. J Plant Physiol 167:430–437
Herrero A, Muro-Pastor AM, Flores E (2001) Nitrogen control in cyanobacteria. J Bacteriol 183:411–425
Holm L, Syer C, Ruterjans H, Schnarr M, Fogh R, Boelens R, Kaptein R (1994) LexA repressor and iron uptake regulator from Escherichia coli: new members of the CAP-like DNA binding domain superfamily. Protein Eng 7:14449–14453
Horsburgh MJ, Ingham E, Foster SJ (2001) In Staphylococcus aureus, Fur is an interactive regulator with PerR, contributes to virulence, and is necessary for oxidative stress resistance through positive regulation of catalase and iron homeostasis. J Bacteriol 183:468–475
Hunt MD, Pettis GS, McIntosh MA (1994) Promoter and operator determinants for Fur-mediated iron regulation in the bidirectional fepA-fes control region of the Escherichia coli enterobactin gene system. J Bacteriol 176:3944–3955
Igarashi J, Kitanishi K, Shimizu T (2011) Emerging roles of heme as a signal and a gas-sensing site: heme sensing and gas-sensing proteins. In: Kadish KM, Smith KM, Guilard R (eds) Handbook of porphyrin science, vol 15. World Scientific Publishing Co, Singapore, pp 399–461
Irieda H, Morita T, Maki K, Homma M, Aiba H, Sudo Y (2012) Photo-induced regulation of the chromatic adaptive gene expression by Anabaena sensory rhodopsin. J Biol Chem 287:32485–32493
Isabella V, Wright LF, Barth K, Spence JM, Grogan S, Genco CA, Clark VL (2008) cis- and trans-acting elements involved in regulation of norB (norZ), the gene encoding nitric oxide reductase in Neisseria gonorrhoeae. Microbiology 154:226–239
Jacquamet L, Traoré DAK, Ferrer J-L, Proux O, Testemale D, Hazemann J-L, Nazarenko E, Ghazouani AE, Caux Thang C, Duarte V, Latour J-M (2009) Structural characterization of the active form of PerR: insights into the metal-induced activation of PerR and Fur proteins for DNA binding. Mol Microbiol 73:20–31
Jacques JF, Jang S, Prevost K, Desnoyers G, Desmarais M, Imlay J, Masse E (2006) RyhB small RNA modulates the free intracellular iron pool and is essential for normal growth during iron limitation in Escherichia coli. Mol Microbiol 62:1181–1190
Jeanjean R, Talla E, Latifi A, Havaux M, Janicki A, Zhang CC (2008) A large gene cluster encoding peptide synthetases and polyketide synthases is involved in production of siderophores and oxidative stress response in the cyanobacterium Anabaena sp. strain PCC 7120. Environ Microbiol 10:2574–2585
Kallifidas D, Pascoe B, Owen GA, Strain-Damerell CM, Hong HJ, Paget MSB (2009) The zinc-responsive regulator zur controls expression of the coelibactin gene cluster in Streptomyces coelicolor. J Bacteriol 192:608–611
Kammler M, Schon C, Hantke K (1993) Characterization of the ferrous iron uptake system of Escherichia coli. J Bacteriol 175:6212–6219
Kaneko T, Sato S, Kotani H, Tanaka A, Asamizu E, Nakamura Y, Miyajima N, Hirosawa M, Sugiura M, Sasamoto S (1996) Sequence analysis of the genome of the unicellular cyanobacterium Synechocystis sp. strain PCC 6803. II. Sequence determination of the entire genome and assignment of potential protein-coding regions. DNA Res 3:109–136
Katayama M, Ohmori M (1997) Isolation and characterization of multiple adenylate cyclase genes from the cyanobacterium Anabaena sp. strain PCC 7120. J Bacteriol 179:3588–3593
Kaushik MS, Srivastava M, Verma E, Mishra AK (2015) Role of manganese in protection against oxidative stress under iron starvation in cyanobacterium Anabaena 7120. J Basic Microbiol 55:729–740
Klebba PE, McIntosh MA, Neilands JB (1982) Kinetics of biosynthesis of iron-regulated membrane proteins in Escherichia coli. J Bacteriol 149:880–888
Kolb A, Busby S, Buc H, Garges S, Adhya S (1993) Transcriptional regulation by cAMP and its receptor protein. Annu Rev Biochem 62:749–795
Krynicka V, Tichý M, Krafl J, Yu J, Kanˇa R, Boehm M, Nixon PJ, Komenda J (2014) Two essential FtsH proteases control the level of the Fur repressor during iron deficiency in the cyanobacterium Synechocystis sp. PCC 6803. Mol Microbiol 94:609–624
Kunert A, Vinnemeier J, Erdmann N, Hagemann M (2003) Repression by Fur is not the main mechanism controlling the iron-inducible isiAB operon in the cyanobacterium Synechocystis sp. PCC 6803. FEMS Microbiol Lett 227:255–262
Latifi A, Ruiz M, Zhang CC (2009) Oxidative stress in cyanobacteria. FEMS Microbiol Rev 33:258–278
Lavrrar JL, Christoffersen CA, McIntosh MA (2003) Fur–DNA interactions at the bidirectional fepDGC-entS promoter region in Escherichia coli. J Mol Biol 322:983–995
Lee HJ, Bang SH, Lee KH, Park SJ (2007) Positive regulation of fur gene expression via direct interaction of fur in a pathogenic bacterium, Vibrio vulnificus. J Bacteriol 189:2629–2636
Lewin AC, Doughty PA, Flegg L, Moore GR, Spiro S (2002) The ferric uptake regulator of Pseudomonas aeruginosa has no essential cysteine residues and does not contain a structural zinc ion. Microbiology 148:2449–2456
Li H, Singh H, McIntyre LM, Sherman LA (2004) Differential gene expression in response to hydrogen peroxide and the putative perR regulon of Synechocystis sp. strain PCC 6803. J Bacteriol 11:3331–3345
Lindsay JA, Foster SJ (2001) zur: a Zn2+-responsive regulatory element of Staphylococcus aureus. Microbiology 147:1259–1266
Litwin CM, Calderwood SB (1994) Analysis of the complexity of gene regulation by fur in Vibrio cholerae. J Bacteriol 176(1):240–248
Litwin M, Boyko SA, Calderwood SB (1992) Cloning, sequencing and transcriptional regulation of the Vibrio cholerae fur gene. J Bacteriol 174:1897–1903
Lopez-Gomollon S, Hernandez JA, Wolk CP, Peleato ML, Fillat MF (2006) Expression of FurA is modulated by NtcA and strongly enhanced in heterocysts of Anabaena sp. PCC 7120. Microbiology 153:42–50
Lopez-Gomollón S, Hernández JA, Pellicer S, Angarica VE, Peleato ML, Fillat MF (2007) Cross-talk between iron and nitrogen regulatory networks in Anabaena (Nostoc) sp. PCC 7120: identification of overlapping genes in furA and ntcA regulons. J Mol Biol 374:267–281
Lopez-Gomollon S, Sevilla S, Bes MT, Peleato ML, Fillat MF (2009) New insights into the role of Fur proteins: Fur (All2473) from Anabaena protects DNA and increases cell survival under oxidative stress. Biochem J 418:201–207
Lukac M, Aegerter R (1993) Influence of trace metals on growth and toxin production of Microcystis aeruginosa. Toxicon 31:293–305
Maciag A, Dainese E, Rodriguez GM, Milano A, Provvedi R, Pasca MR, Smith I, Palu G, Riccardi G, Manganelli R (2007) Global analysis of the Mycobacterium tuberculosis Zur (FurB) regulon. J Bacteriol 189:730–740
Martin-Luna B, Hernandez JA, Bes MT, Fillat MF, Peleato ML (2005) Identification of a Ferric uptake regulator (Fur) from Microcystis aeruginosa PCC 7806. FEMS Microbiol Lett 254:63–70
Martin-Luna B, Sevilla E, Hernandez JA, Bes MT, Fillat MF, Peleato ML (2006) Fur from Microcystis aeruginosa binds in vitro promoter regions of the microcystin biosynthesis gene cluster. Phytochemistry 67:876–881
Martin-Luna B, Sevilla E, Gonzalez A, Bes MT, Fillat MF, Peleato ML (2011) Expression of fur and its antisense fur from Microcystis aeruginosa PCC 7806 as response to light and oxidative stress. J Plant Physiol 168:2244–2250
Masse E, Gottesman S (2002) A small RNA regulates the expression of genes involved in iron metabolism in Escherichia coli. Proc Natl Acad Sci 99:4620–4625
Masse E, Majdalani N, Gottesman S (2003) Regulatory roles for small RNAs in bacteria. Curr Opin Microbiol 6:120–124
Masse E, Vanderpool CK, Gottesman S (2005) Effect of RyhB small RNA on global iron use in Escherichia coli. J Bacteriol 187:6962–6971
Masse E, Salvail H, Desnoyers G, Arguin M (2007) Small RNAs controlling iron metabolism. Curr Opin Microbiol 10(2):140–145
Mellin JR, Goswami S, Grogan S, Tjaden B, Genco CA (2007) A novel Fur- and iron-regulated small RNA, NrrF, is required for indirect Fur mediated regulation of the sdhA and sdhC genes in Neisseria meningitidis. J Bacteriol 189:3686–3694
Mellin JR, McClure R, Lopez D, Green O, Reinhard B, Genco C (2010) Role of Hfq in iron-dependent and –independent gene regulation in Neisseria meningitidis. Microbiology 156:2316–2326
Mey AR, Craig SA, Payne SM (2005) Characterization of Vibrio cholerae RyhB: the RyhB regulon and role of ryhB in biofilm formation. Infect Immun 73:5706–5719
Meyer JM (2000) Pyoverdins: pigments, siderophores and potential taxonomic markers of fluorescent Pseudomonas species. Arch Microbiol 174:135–142
Michaud-Soret I, Adrait A, Jaquinod M, Forest E, Touati D, Latour JM (1997) Electrospray ionization mass spectroscopy analysis of theapo- and metal-substituted forms of the Fur protein. FEBS Lett 413:473–476
Michel KP, Kruger F, Puhler A, Pistorius EK (1999) Molecular characterization of idiA and adjacent genes in the cyanobacteria Synechococcus sp. strains PCC 6301 and PCC 7942. Microbiology 145:1473–1484
Miles S, Carpenter BM, Gancz H, Merrell DS (2010) Helicobacter pylori apo-Fur regulation appears unconserved across species. J Microbiol 48:378–386
Mills SA, Marletta MA (2005) Metal binding characteristics and role of iron oxidation in the ferric uptake regulator from Escherichia coli. Biochemistry 44:13553–13559
Nandal A, Huggins CC, Woodhall MR, McHugh J, Rodriguez-Quinones F, Quail MA (2010) Induction of the ferritin gene (ftnA) of Escherichia coli by Fe2+-Fur is mediated by reversal of H-NS silencing and is RyhB independent. Mol Microbiol 75:637–657
Napolitano M, Rubio MÁ, Santamaría-Gómez J, Olmedo-Verd E, Robinson NJ, Luque I (2012) Characterization of the response to zinc deficiency in the cyanobacterium Anabaena sp. Strain PCC 7120. J Bacteriol 194:2426–2436
Neilands JB, Nakamura K (1991) Detection, determination, isolation, characterization and regulation of microbial iron chelates. In: Winkelmann G (ed) Handbook of microbial iron chelates. CRC Press, Boca Raton, pp 1–14
Ogawa K, Sun J, Taketani S, Nakajima O, Nishitani C, Sassa S, Hayashi N, Yamamoto M, Shibahara S, Fujita H (2001) Heme mediates derepression of Maf recognition element through direct binding to transcription repressor Bach1. EMBO J 20:2835–2843
Okamoto S, Kasahara M, Kamiya A, Nakahira Y, Ohmori M (2004) A phytochrome-like protein AphC triggers the cAMP signaling induced by far-red light in the cyanobacterium Anabaena sp. strain PCC7120. Photochem Photobiol 80:429–433
Ortiz de Orue Lucana D, Schrempf H (2000) The DNA-binding characteristics of the Streptomyces reticuli regulator FurS depend on the redox state of its cysteine residues. Mol Gen Genet 264:341–353
Paerl HW, Fulton RS, Moisander PH (2001) Harmful freshwater algal blooms, with an emphasis on cyanobacteria. Sci World 1:76–113
Paoli M, Marles-Wright J, Smith A (2002) Structure–function relationships in heme-proteins. DNA Cell Biol 21:271–280
Patzer SI (2000) The zinc-responsive regulator Zur and its control of the znu gene cluster encoding the ZnuABC zinc uptake system in Escherichia coli. J Biol Chem 275:24321–24332
Pellicer S, Gonzalez A, Peleato ML, Martinez JI, Fillat MF, Bes MT (2012) Site-directed mutagenesis and spectral studies suggest a putative role of FurA from Anabaena sp. PCC 7120 as a heme sensor protein. FEBS J 279:2231–2246
Pohl E, Holmes RK, Hol WGJ (1999) Crystal structure of a cobalt-activated diphtheria toxin repressor–DNA complex reveals a metal-binding SH3-like domain. J Mol Biol 292:653–667
Pohl E, Haller JC, Mijovilovich A, Meyer-Klaucke W, Garman E, Vasil ML (2003) Architecture of a protein central to iron homeostasis: crystal structure and spectroscopic analysis of the ferric uptake regulator. Mol Microbiol 47:903–915
Pressler U, Staudenmaier H, Zimmermann L, Braun V (1988) Genetics of the iron dicitrate transport system of Escherichia coli. J Bacteriol 170:2716–2724
Quan S, Schneider I, Pan J, Von Hacht A, Bardwell JC (2007) The CXXC motif is more than a redox rheostat. J Biol Chem 282:28823–28833
Rueter JG, Petersen RR (1987) Micronutrient effects on cyanobacterial growth and physiology. N Z J Mar Freshw Res 21:435–445
Saito T, Williams RJP (1991) The binding of the ferric uptake regulation protein to a DNA fragment. Eur J Biochem 197:43–47
Saito I, Wormald MR, Williams RJP (1991) Some structural features of the iron-uptake regulation protein. Eur J Biochem 197:29–38
Salinas PC, Tolmasky ME, Crosa JH (1989) Regulation of the iron uptake system in Vibrio anguillarum: evidence for a cooperative effect between two transcriptional activators. Proc Natl Acad Sci U S A 86:3529–3533
Sebastian S, Agarwal S, Murphy JR, Genco CA (2002) The gonococcal fur regulon: identification of additional genes involved in major catabolic, recombination, and secretory pathways. J Bacteriol 184:3965–3974
Sein-Echaluce VC, González A, Napolitano M, Luque I, Barja F, Peleato ML, Fillat MF (2014) Zur (FurB) is a key factor in the control of the oxidative stress response in Anabaena sp. PCC 7120. Environ Microbiol. doi:10.1111/1462-2920.12628
Sevier CS, Kaiser CA (2002) Formation and transfer of disulphide bonds in living cells. Nat Rev Mol Cell Biol 3:836–847
Sheikh MA, Taylor GL (2009) Crystal structure of the Vibrio cholerae ferric uptake regulator (Fur) reveals insights into metal co-ordination. Mol Microbiol 72:1208–1220
Singh AK, McIntyre LM, Sherman LA (2003) Microarray analysis of the genome-wide response to iron deficiency and iron reconstitution in the cyanobacterium Synechocystis sp. PCC 6803. Plant Physiol 132:1825–1839
Singh A, Mishra AK, Singh SS, Shukla E (2008) Influence of iron and chelator on siderophore production in Frankia strains nodulating Hippopheae salicifolia D. Don. J Basic Microbiol 48:104–111
Singh A, Singh SS, Pandey PC, Mishra AK (2010) Attenuation of metal toxicity by Frankial siderophores. Toxicol Environ Chem 92:1339–1346
Smith A, Hooper NI, Shipulina N, Morgan WT (1996) Heme binding by a bacterial repressor protein, the gene product of the ferric uptake regulation (Fur) gene of Escherichia coli. J Protein Chem 15:575–583
Somerville G, Mikoryak CA, Reitzer L (1999) Physiological characterization of Pseudomonas aeruginosa during exotoxin A synthesis: glutamate, iron limitation, and aconitase activity. J Bacteriol 181:1072–1078
Stojiljkovic I, Hantke K (1995) Functional domains of the Escherichia coli ferric uptake regulator protein (Fur). Mol Gen Genet 247:199–205
Stojiljkovic I, Baumler AJ, Hantke K (1994) Fur regulon in Gram negative bacteria. Identification and characterization of new iron-regulated Escherichia coli genes by a Fur titration assay. J Mol Biol 236:531–545
Straus NA (1994) Iron deprivation: physiology and gene regulation. In: Bryant DA (ed) The molecular biology of cyanobacteria. Kluwer academic publisher, Netherlands, pp 731–750
Teixido L, Carrasco B, Alonso JC, Barbe J, Campoy S (2011) Fur activates the expression of Salmonella enterica pathogenicity island 1 by directly interacting with the hilD operator in vivo and in vitro. PLoS One 6, e19711
Thompson DK, Beliaev AS, Giometti CS, Tollaksen SL, Khare T, Lies DP, Nealson KH, Lim H, Yates J, Brandt CC, Tiedje JM, Zhou J (2002) Transcriptional and proteomic analysis of a Ferric Uptake Regulator (Fur) mutant of Shewanella oneidensis: possible involvement of Fur in energy metabolism, transcriptional regulation, and oxidative stress. Appl Environ Microbiol 68:881–892
Touati D (2000) Iron and oxidative stress in bacteria. Arch Biochem Biophys 373:1–6
Utkilen H, Gjolme N (1995) Iron-stimulated toxin production in Microcystis aeruginosa. Appl Environ Microbiol 61(2):797–800
Wang Y, Zhang X, Feng S, Niu Z, Chen C (2009) Study on inactivation of iron bacteria isolated from real drinking water distribution systems by free chlorine and chloramines. Ann Microbiol 59(2):353–358
Wang Y, Mo X, Zhang L, Wang Q (2011) Four superoxide dismutase (isozymes) genes of Bacillus cereus. Ann Microbiol 61:355–360
Wee S, Neilands JB, Bittner ML, Hemming BC, Haymore BL, Seetharam R (1988) Expression, isolation and properties of Fur (ferric uptake regulation) protein of Escherichia coli K-12. Biol Metals 1:62–68
White A, Ding X, vander Spek JC, Murphy JR, Ringe D (1998) Structure of the metal-ion-activated diphtheria toxin repressor/tox operator complex. Nature 394:502–506
Wilderman PJ, Sowa NA, FitzGerald DJ, FitzGerald PC, Gottesman S, Ochsner UA, Vasil ML (2004) Identification of tandem duplicate regulatory small RNAs in Pseudomonas aeruginosa involved in iron homeostasis. Proc Natl Acad Sci 101:9792–9797
Xiong A, Singh VK, Cabrera G, Jayaswal RK (2000) Molecular characterization of the ferric-uptake regulator, Fur, from Staphylococcus aureus. Microbiology 146:659–668
Yingping F, Lemeille S, Talla E, Janicki A, Denis Y, Zhang C-C, Latifi A (2014) Unravelling the cross-talk between iron starvation and oxidative stress responses highlights the key role of PerR (alr0957) in peroxide signalling in the cyanobacterium Nostoc PCC 7120. Environ Microbiol Rep 6:468–475
Yu C, Genco CA (2012) Fur mediated global regulatory circuit in pathogenic Neisseria species. J Bacteriol 194:6372–6381
Zhang L, Guarente L (1995) Heam binds to a short sequence that serves a regulatory function in diverse proteins. EMBO J 14:313–320
Zheleznova EE, Crosa JH, Brennan RG (2000) Characterization of the DNA- and metal-binding properties of Vibrio anguillarum Fur reveals conservation of a structural Zn2+ ion. J Bacteriol 182:6264–6267
Zheng M, Doan B, Schneider TD, Storz G (1999) OxyR and SoxRS regulation of Fur. J Bacteriol 181:4639–4643
Zhou D, Qin L, Han Y, Qiu J, Chen Z, Li B, Song Y, Wang J, Guo Z, Zhai J, Du Z, Wang X, Yang R (2006) Global analysis of iron assimilation and Fur regulation in Yersinia pestis. FEMS Microbiol Lett 258:9–17
Zou P, Borovok I, Ortiz de Orué Lucana D, Müller D, Schrempf H (1999) The mycelium-associated Streptomyces reticuli catalase-peroxidase, its gene and regulation by FurS. Microbiology 145:549–559
Acknowledgments
We are thankful to the Council of Scientific and Industrial Research, New Delhi for providing financial support. The Head of the Department of Botany, Banaras Hindu University, Varanasi, India is gratefully acknowledged for providing the laboratory facility.
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Kaushik, M.S., Singh, P., Tiwari, B. et al. Ferric Uptake Regulator (FUR) protein: properties and implications in cyanobacteria. Ann Microbiol 66, 61–75 (2016). https://doi.org/10.1007/s13213-015-1134-x
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DOI: https://doi.org/10.1007/s13213-015-1134-x