Ferric uptake regulator family explained

Symbol:FUR
FUR
Pfam:PF01475
Pfam Clan:CL0123
Interpro:IPR002481
Scop:1mzb
Ferric uptake regulatory protein
Organism:Escherichia coli
Taxid:83333
Symbol:Fur
Pdb:2FU4
Uniprot:P0A9A9

In molecular biology, the ferric uptake regulator family is a family of bacterial proteins involved in regulating metal ion uptake and in metal homeostasis. The family is named for its founding member, known as the ferric uptake regulator or ferric uptake regulatory protein (Fur). Fur proteins are responsible for controlling the intracellular concentration of iron in many bacteria. Iron is essential for most organisms, but its concentration must be carefully managed over a wide range of environmental conditions; high concentrations can be toxic due to the formation of reactive oxygen species.[1]

Function

Members of the ferric uptake regulator family are transcription factors that primarily exert their regulatory effects as repressors: when bound to their cognate metal ion, they are capable of binding DNA and preventing expression of the genes they regulate, but under low concentrations of metal, they undergo a conformational change that prevents DNA binding and lifts the repression.[2] [3] In the case of the ferric uptake regulator protein itself, its immediate downstream target is a noncoding RNA called RyhB.

In addition to the ferric uptake regulator protein, members of the Fur family are also involved in maintaining homeostasis with respect to other ions:[4]

The iron dependent repressor family is a functionally similar but non-homologous family of proteins involved in iron homeostasis in prokaryotes.

Relationship to virulence

Metal homeostasis can be a factor in bacterial virulence, an observation with a particularly long history in the case of iron.[15] [16] [17] In some cases, expression of virulence factors is under the regulatory control of the Fur protein.

Notes and References

  1. Pohl E, Haller JC, Mijovilovich A, Meyer-Klaucke W, Garman E, Vasil ML . Architecture of a protein central to iron homeostasis: crystal structure and spectroscopic analysis of the ferric uptake regulator . Molecular Microbiology . 47 . 4 . 903–15 . February 2003 . 12581348 . 10.1046/j.1365-2958.2003.03337.x . 38938808 . free .
  2. Porcheron G, Dozois CM . Interplay between iron homeostasis and virulence: Fur and RyhB as major regulators of bacterial pathogenicity . Veterinary Microbiology . 179 . 1–2 . 2–14 . August 2015 . 25888312 . 10.1016/j.vetmic.2015.03.024 . free .
  3. Gilston BA, Wang S, Marcus MD, Canalizo-Hernández MA, Swindell EP, Xue Y, Mondragón A, O'Halloran TV . Structural and mechanistic basis of zinc regulation across the E. coli Zur regulon . PLOS Biology . 12 . 11 . e1001987 . November 2014 . 25369000 . 4219657 . 10.1371/journal.pbio.1001987 . free .
  4. Waldron KJ, Robinson NJ . How do bacterial cells ensure that metalloproteins get the correct metal? . Nature Reviews. Microbiology . 7 . 1 . 25–35 . January 2009 . 19079350 . 10.1038/nrmicro2057 . 7253420 .
  5. Díaz-Mireles E, Wexler M, Sawers G, Bellini D, Todd JD, Johnston AW . The Fur-like protein Mur of Rhizobium leguminosarum is a Mn(2+)-responsive transcriptional regulator . Microbiology . 150 . Pt 5 . 1447–56 . May 2004 . 15133106 . 10.1099/mic.0.26961-0 . free .
  6. Platero R, Peixoto L, O'Brian MR, Fabiano E . Fur is involved in manganese-dependent regulation of mntA (sitA) expression in Sinorhizobium meliloti . Applied and Environmental Microbiology . 70 . 7 . 4349–55 . July 2004 . 15240318 . 444773 . 10.1128/AEM.70.7.4349-4355.2004 . 2004ApEnM..70.4349P .
  7. Chao TC, Becker A, Buhrmester J, Pühler A, Weidner S . The Sinorhizobium meliloti fur gene regulates, with dependence on Mn(II), transcription of the sitABCD operon, encoding a metal-type transporter . Journal of Bacteriology . 186 . 11 . 3609–20 . June 2004 . 15150249 . 415740 . 10.1128/JB.186.11.3609-3620.2004 .
  8. Hohle TH, O'Brian MR . The mntH gene encodes the major Mn(2+) transporter in Bradyrhizobium japonicum and is regulated by manganese via the Fur protein . Molecular Microbiology . 72 . 2 . 399–409 . April 2009 . 19298371 . 2675660 . 10.1111/j.1365-2958.2009.06650.x .
  9. Menscher EA, Caswell CC, Anderson ES, Roop RM . Mur regulates the gene encoding the manganese transporter MntH in Brucella abortus 2308 . Journal of Bacteriology . 194 . 3 . 561–6 . February 2012 . 22101848 . 3264066 . 10.1128/JB.05296-11 .
  10. Ahn BE, Cha J, Lee EJ, Han AR, Thompson CJ, Roe JH . Nur, a nickel-responsive regulator of the Fur family, regulates superoxide dismutases and nickel transport in Streptomyces coelicolor . Molecular Microbiology . 59 . 6 . 1848–58 . March 2006 . 16553888 . 10.1111/j.1365-2958.2006.05065.x . 2728024 . free .
  11. Lee JW, Helmann JD . The PerR transcription factor senses H2O2 by metal-catalysed histidine oxidation . Nature . 440 . 7082 . 363–7 . March 2006 . 16541078 . 10.1038/nature04537 . 2006Natur.440..363L . 4390980 .
  12. Graham AI, Hunt S, Stokes SL, Bramall N, Bunch J, Cox AG, McLeod CW, Poole RK . Severe zinc depletion of Escherichia coli: roles for high affinity zinc binding by ZinT, zinc transport and zinc-independent proteins . The Journal of Biological Chemistry . 284 . 27 . 18377–89 . July 2009 . 19377097 . 2709383 . 10.1074/jbc.M109.001503 . free .
  13. Blindauer CA . Advances in the molecular understanding of biological zinc transport . Chemical Communications . 51 . 22 . 4544–63 . March 2015 . 25627157 . 10.1039/c4cc10174j . free .
  14. O'Brian MR . Perception and Homeostatic Control of Iron in the Rhizobia and Related Bacteria . Annual Review of Microbiology . 69 . 229–45 . 2015 . 26195304 . 10.1146/annurev-micro-091014-104432 .
  15. Book: Bullen JJ, Rogers HJ, Griffiths E . Modern Aspects of Electrochemistry . Role of Iron in Bacterial Infection . Current Topics in Microbiology and Immunology . 80 . 1–35 . 1978 . 10.1007/978-3-642-66956-9_1 . 352628 . 978-1-4612-9003-2 .
  16. Ratledge C, Dover LG . Iron metabolism in pathogenic bacteria . Annual Review of Microbiology . 54 . 881–941 . 2000 . 11018148 . 10.1146/annurev.micro.54.1.881 .
  17. Litwin CM, Calderwood SB . Role of iron in regulation of virulence genes . Clinical Microbiology Reviews . 6 . 2 . 137–49 . April 1993 . 8472246 . 358274 . 10.1128/cmr.6.2.137 .

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