Ferric uptake regulator family

Last updated
Magnetospirillum gryphiswaldense
Magnetospirillum gryphiswaldense.jpg
Binding Site 1 within FUR
Identifiers
SymbolFUR
SCOP2 4RB1 / SCOPe / SUPFAM
FUR
PDB 1mzb EBI.jpg
ferric uptake regulator
Identifiers
SymbolFUR
Pfam PF01475
Pfam clan CL0123
InterPro IPR002481
SCOP2 1mzb / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
Ferric uptake regulatory protein
Identifiers
Organism Escherichia coli
SymbolFur
PDB 2FU4
UniProt P0A9A9
Search for
Structures Swiss-model
Domains InterPro

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]

Contents

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. [2]

The Ferric Uptake Regulator protein functions in Gram-negative and Gram-positive bacteria. Ferric uptake regulators act by sensing changes in free iron, so upon activation, they regulate target genes through interactions with the promoter region, known as the "Fur box". The magnetospirillum gryphiswaldense MSR-1 Fur is a key regulatory protein involved in maintaining iron homeostasis. This Fur is similar to the E. coli Fur, which acts by binding to Fur boxes to regulate gene expression as a way to maintain iron levels. Additionally, it serves as a model and foundation for other regulators that are able to sense changes in iron, zinc, and magnesium.

In the image of the binding sites of magnetospirillum gryphiswaldense, the cyan color reflects the glutamate residues, while the magenta represents the histidine residues. These residues interact with the manganese ion to create binding site 1 in the ferric uptake regulator protein.

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. [1]

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. [1] [2]

References

  1. 1 2 3 Pohl E, Haller JC, Mijovilovich A, Meyer-Klaucke W, Garman E, Vasil ML (February 2003). "Architecture of a protein central to iron homeostasis: crystal structure and spectroscopic analysis of the ferric uptake regulator". Molecular Microbiology. 47 (4): 903–15. doi: 10.1046/j.1365-2958.2003.03337.x . PMID   12581348. S2CID   38938808.
  2. 1 2 3 Porcheron G, Dozois CM (August 2015). "Interplay between iron homeostasis and virulence: Fur and RyhB as major regulators of bacterial pathogenicity". Veterinary Microbiology. 179 (1–2): 2–14. doi: 10.1016/j.vetmic.2015.03.024 . PMID   25888312.
  3. ↑ Gilston BA, Wang S, Marcus MD, Canalizo-Hernández MA, Swindell EP, Xue Y, Mondragón A, O'Halloran TV (November 2014). "Structural and mechanistic basis of zinc regulation across the E. coli Zur regulon". PLOS Biology. 12 (11): e1001987. doi: 10.1371/journal.pbio.1001987 . PMC   4219657 . PMID   25369000.
  4. ↑ Waldron KJ, Robinson NJ (January 2009). "How do bacterial cells ensure that metalloproteins get the correct metal?". Nature Reviews. Microbiology. 7 (1): 25–35. doi:10.1038/nrmicro2057. PMID   19079350. S2CID   7253420.
  5. ↑ Díaz-Mireles E, Wexler M, Sawers G, Bellini D, Todd JD, Johnston AW (May 2004). "The Fur-like protein Mur of Rhizobium leguminosarum is a Mn(2+)-responsive transcriptional regulator". Microbiology. 150 (Pt 5): 1447–56. doi: 10.1099/mic.0.26961-0 . PMID   15133106.
  6. ↑ Platero R, Peixoto L, O'Brian MR, Fabiano E (July 2004). "Fur is involved in manganese-dependent regulation of mntA (sitA) expression in Sinorhizobium meliloti". Applied and Environmental Microbiology. 70 (7): 4349–55. Bibcode:2004ApEnM..70.4349P. doi:10.1128/AEM.70.7.4349-4355.2004. PMC   444773 . PMID   15240318.
  7. ↑ Chao TC, Becker A, Buhrmester J, Pühler A, Weidner S (June 2004). "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. doi:10.1128/JB.186.11.3609-3620.2004. PMC   415740 . PMID   15150249.
  8. ↑ Hohle TH, O'Brian MR (April 2009). "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. doi:10.1111/j.1365-2958.2009.06650.x. PMC   2675660 . PMID   19298371.
  9. ↑ Menscher EA, Caswell CC, Anderson ES, Roop RM (February 2012). "Mur regulates the gene encoding the manganese transporter MntH in Brucella abortus 2308". Journal of Bacteriology. 194 (3): 561–6. doi:10.1128/JB.05296-11. PMC   3264066 . PMID   22101848.
  10. ↑ Ahn BE, Cha J, Lee EJ, Han AR, Thompson CJ, Roe JH (March 2006). "Nur, a nickel-responsive regulator of the Fur family, regulates superoxide dismutases and nickel transport in Streptomyces coelicolor". Molecular Microbiology. 59 (6): 1848–58. doi: 10.1111/j.1365-2958.2006.05065.x . PMID   16553888. S2CID   2728024.
  11. ↑ Lee JW, Helmann JD (March 2006). "The PerR transcription factor senses H2O2 by metal-catalysed histidine oxidation". Nature. 440 (7082): 363–7. Bibcode:2006Natur.440..363L. doi:10.1038/nature04537. PMID   16541078. S2CID   4390980.
  12. ↑ Graham AI, Hunt S, Stokes SL, Bramall N, Bunch J, Cox AG, McLeod CW, Poole RK (July 2009). "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. doi: 10.1074/jbc.M109.001503 . PMC   2709383 . PMID   19377097.
  13. ↑ Blindauer CA (March 2015). "Advances in the molecular understanding of biological zinc transport" (PDF). Chemical Communications. 51 (22): 4544–63. doi: 10.1039/c4cc10174j . PMID   25627157.
  14. ↑ O'Brian MR (2015). "Perception and Homeostatic Control of Iron in the Rhizobia and Related Bacteria". Annual Review of Microbiology. 69: 229–45. doi:10.1146/annurev-micro-091014-104432. PMID   26195304.
  15. ↑ Bullen JJ, Rogers HJ, Griffiths E (1978). "Role of Iron in Bacterial Infection". Modern Aspects of Electrochemistry. Current Topics in Microbiology and Immunology. Vol. 80. pp. 1–35. doi:10.1007/978-3-642-66956-9_1. ISBN   978-1-4612-9003-2. PMID   352628.
  16. ↑ Ratledge C, Dover LG (2000). "Iron metabolism in pathogenic bacteria". Annual Review of Microbiology. 54: 881–941. doi:10.1146/annurev.micro.54.1.881. PMID   11018148.
  17. ↑ Kim, Jeong (2016). "Roles of two RyhB paralogs in the physiology of Salmonella enterica". Science Direct.
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