iron binding proteins


Summary: Proteins that specifically bind to IRON.

Top Publications

  1. Karlberg T, Schagerlöf U, Gakh O, Park S, Ryde U, Lindahl M, et al. The structures of frataxin oligomers reveal the mechanism for the delivery and detoxification of iron. Structure. 2006;14:1535-46 pubmed
    ..The data reveal how stepwise assembly provides frataxin with the structural flexibility to perform two functions: metal delivery and detoxification. ..
  2. Baralle M, Pastor T, Bussani E, Pagani F. Influence of Friedreich ataxia GAA noncoding repeat expansions on pre-mRNA processing. Am J Hum Genet. 2008;83:77-88 pubmed publisher
  3. Li K, Besse E, Ha D, Kovtunovych G, Rouault T. Iron-dependent regulation of frataxin expression: implications for treatment of Friedreich ataxia. Hum Mol Genet. 2008;17:2265-73 pubmed publisher
    ..Thus, our results imply that therapeutic efforts should focus on an approach that combines iron removal from mitochondria with a treatment that increases cytosolic iron levels to maximize residual frataxin expression in FA patients. ..
  4. Lu C, Cortopassi G. Frataxin knockdown causes loss of cytoplasmic iron-sulfur cluster functions, redox alterations and induction of heme transcripts. Arch Biochem Biophys. 2007;457:111-22 pubmed
  5. Herman D, Jenssen K, Burnett R, Soragni E, Perlman S, Gottesfeld J. Histone deacetylase inhibitors reverse gene silencing in Friedreich's ataxia. Nat Chem Biol. 2006;2:551-8 pubmed
    ..This class of HDAC inhibitors may yield therapeutics for Friedreich's ataxia...
  6. Llorens J, Navarro J, Martínez Sebastián M, Baylies M, Schneuwly S, Botella J, et al. Causative role of oxidative stress in a Drosophila model of Friedreich ataxia. FASEB J. 2007;21:333-44 pubmed
    ..We propose that in FA, the oxidative mediated inactivation of aconitase, which occurs normally during the aging process, is enhanced due to the lack of frataxin. ..
  7. De Biase I, Rasmussen A, Monticelli A, Al Mahdawi S, Pook M, Cocozza S, et al. Somatic instability of the expanded GAA triplet-repeat sequence in Friedreich ataxia progresses throughout life. Genomics. 2007;90:1-5 pubmed
    ..91; p=0.0001). Therefore, somatic instability in FRDA occurs mostly after early embryonic development and progresses throughout life, lending further support to the role of postnatal somatic instability in disease pathogenesis. ..
  8. Vivas E, Skovran E, Downs D. Salmonella enterica strains lacking the frataxin homolog CyaY show defects in Fe-S cluster metabolism in vivo. J Bacteriol. 2006;188:1175-9 pubmed
    ..When present in combination with other lesions, mutations in cyaY can result in a strain with more severe defects than those lacking the isc locus. ..
  9. Martelli A, Wattenhofer Donzé M, Schmucker S, Bouvet S, Reutenauer L, Puccio H. Frataxin is essential for extramitochondrial Fe-S cluster proteins in mammalian tissues. Hum Mol Genet. 2007;16:2651-8 pubmed
    ..These results thus provide new cellular pathways that may contribute to molecular mechanisms of the disease. ..

More Information


  1. Strickler Dinglasan P, Guz N, Attardo G, Aksoy S. Molecular characterization of iron binding proteins from Glossina morsitans morsitans (Diptera: Glossinidae). Insect Biochem Mol Biol. 2006;36:921-33 pubmed
    ..On the other hand, GmmFer1HCH maintains both the conserved ferroxidase center and the 5'UTR IRE; however, transcript variants suggest a more extensive regulatory mechanism for this subunit. ..
  2. Grant L, Sun J, Xu H, Subramony S, Chaires J, Hebert M. Rational selection of small molecules that increase transcription through the GAA repeats found in Friedreich's ataxia. FEBS Lett. 2006;580:5399-405 pubmed
    ..One of these compounds, pentamidine, increases frataxin levels in patient cells. Thus our approach can be used to detect small molecules of potential therapeutic value in FRDA. ..
  3. Al Mahdawi S, Pinto R, Varshney D, Lawrence L, Lowrie M, Hughes S, et al. GAA repeat expansion mutation mouse models of Friedreich ataxia exhibit oxidative stress leading to progressive neuronal and cardiac pathology. Genomics. 2006;88:580-90 pubmed
    ..These mice represent the first GAA repeat expansion-based FRDA mouse models that exhibit progressive FRDA-like pathology and thus will be of use in testing potential therapeutic strategies, particularly GAA repeat-based strategies. ..
  4. Khan A, Shouldice S, Tari L, Schryvers A. The role of the synergistic phosphate anion in iron transport by the periplasmic iron-binding protein from Haemophilus influenzae. Biochem J. 2007;403:43-8 pubmed
    ..The results suggest that the transport of iron by FbpA is not dependent on binding of phosphate in the synergistic anion-binding site. ..
  5. De Biase I, Rasmussen A, Endres D, Al Mahdawi S, Monticelli A, Cocozza S, et al. Progressive GAA expansions in dorsal root ganglia of Friedreich's ataxia patients. Ann Neurol. 2007;61:55-60 pubmed
    ..Progressive repeat expansion in specific tissues is a common theme in the pathogenesis of triplet-repeat diseases. ..
  6. Shan Y, Napoli E, Cortopassi G. Mitochondrial frataxin interacts with ISD11 of the NFS1/ISCU complex and multiple mitochondrial chaperones. Hum Mol Genet. 2007;16:929-41 pubmed
    ..These data suggest that frataxin binds the iron-sulfur biogenesis Nfs1/ISCU complex through ISD11, that the interaction is nickel-dependent, and that multiple consequences of frataxin deficiency are duplicated by ISD11 deficiency...
  7. Ikeguchi M, Ueno J, Sato M, Kidera A. Protein structural change upon ligand binding: linear response theory. Phys Rev Lett. 2005;94:078102 pubmed
  8. O Neill H, Gakh O, Park S, Cui J, Mooney S, Sampson M, et al. Assembly of human frataxin is a mechanism for detoxifying redox-active iron. Biochemistry. 2005;44:537-45 pubmed
    ..In contrast, the assembled protein has ferroxidase activity and detoxifies redox-active iron by sequestering it in a protein-protected compartment. ..
  9. Xu C, Soragni E, Chou C, Herman D, Plasterer H, Rusche J, et al. Chemical probes identify a role for histone deacetylase 3 in Friedreich's ataxia gene silencing. Chem Biol. 2009;16:980-9 pubmed publisher
    ..Additional inhibitors with different HDAC specificity profiles were synthesized, and results from transcription experiments in FRDA cells point to a unique role for HDAC3 in gene silencing in Friedreich's ataxia. ..
  10. Huang M, Becker E, Whitnall M, Suryo Rahmanto Y, Ponka P, Richardson D. Elucidation of the mechanism of mitochondrial iron loading in Friedreich's ataxia by analysis of a mouse mutant. Proc Natl Acad Sci U S A. 2009;106:16381-6 pubmed publisher
    ..Our results enable the construction of a model explaining the cytosolic iron deficiency and mitochondrial iron loading in the absence of frataxin, which is important for understanding the pathogenesis of Friedreich's ataxia. ..
  11. Napoli E, Morin D, Bernhardt R, Buckpitt A, Cortopassi G. Hemin rescues adrenodoxin, heme a and cytochrome oxidase activity in frataxin-deficient oligodendroglioma cells. Biochim Biophys Acta. 2007;1772:773-80 pubmed
  12. Aloria K, Schilke B, Andrew A, Craig E. Iron-induced oligomerization of yeast frataxin homologue Yfh1 is dispensable in vivo. EMBO Rep. 2004;5:1096-101 pubmed
    ..Rather, the capacity of this oligomerization-deficient mutant to interact with the Isu protein suggests a more direct role of Yfh1 in iron-sulphur cluster biogenesis. ..
  13. Grabczyk E, Mancuso M, Sammarco M. A persistent RNA.DNA hybrid formed by transcription of the Friedreich ataxia triplet repeat in live bacteria, and by T7 RNAP in vitro. Nucleic Acids Res. 2007;35:5351-9 pubmed
    ..TTC tracts. RNA.DNA hybrids have a potential role in GAA.TTC tract instability and in the mechanism underlying reduced frataxin mRNA levels in Friedreich Ataxia. ..
  14. Boesch S, Sturm B, Hering S, Goldenberg H, Poewe W, Scheiber Mojdehkar B. Friedreich's ataxia: clinical pilot trial with recombinant human erythropoietin. Ann Neurol. 2007;62:521-4 pubmed
    ..Treatment with recombinant human erythropoietin showed a persistent and significant increase in frataxin levels after 8 weeks (p < 0.01). All patients showed a reduction of oxidative stress markers...
  15. Gellera C, Castellotti B, Mariotti C, Mineri R, Seveso V, DiDonato S, et al. Frataxin gene point mutations in Italian Friedreich ataxia patients. Neurogenetics. 2007;8:289-99 pubmed
    ..01) correlation was observed between the size of GAA expansion and the age at onset, thus lending support to the hypothesis that the residual function of frataxin in patients' cells derive exclusively from the expanded allele. ..
  16. Pollard L, Bourn R, Bidichandani S. Repair of DNA double-strand breaks within the (GAA*TTC)n sequence results in frequent deletion of the triplet-repeat sequence. Nucleic Acids Res. 2008;36:489-500 pubmed
    ..Our data contrast significantly with DSB repair within (CTG*CAG)n repeats, indicating that repair-mediated instability is dependent on the sequence of the triplet repeat. ..
  17. Anderson P, Kirby K, Orr W, Hilliker A, Phillips J. Hydrogen peroxide scavenging rescues frataxin deficiency in a Drosophila model of Friedreich's ataxia. Proc Natl Acad Sci U S A. 2008;105:611-6 pubmed publisher
    ..The therapeutic implications of these findings are clear and we believe warrant immediate clinical investigation. ..
  18. Pandolfo M. Friedreich ataxia: the clinical picture. J Neurol. 2009;256 Suppl 1:3-8 pubmed publisher
    ..In addition to a review of the clinicopathological features of FRDA, a discussion of recent advances in our understanding of the underlying molecular mechanisms is provided. ..
  19. Ventura N, Rea S, Testi R. Long-lived C. elegans mitochondrial mutants as a model for human mitochondrial-associated diseases. Exp Gerontol. 2006;41:974-91 pubmed
    ..The identification of such compensatory pathways opens a window of possibility for future preventative therapies for many HMADs. They may also provide a way of potentially extending human life span. ..
  20. Condo I, Ventura N, Malisan F, Tomassini B, Testi R. A pool of extramitochondrial frataxin that promotes cell survival. J Biol Chem. 2006;281:16750-6 pubmed
    ..Remarkably, extramitochondrial frataxin can fully replace mitochondrial frataxin in promoting survival of FA cells...
  21. Schoenfeld R, Napoli E, Wong A, Zhan S, Reutenauer L, Morin D, et al. Frataxin deficiency alters heme pathway transcripts and decreases mitochondrial heme metabolites in mammalian cells. Hum Mol Genet. 2005;14:3787-99 pubmed
    ..As ataxic symptoms occur in other diseases of heme deficiency, the heme defect we observe in frataxin-deficient cells could be primary to the pathophysiological process. ..
  22. Gottesfeld J. Small molecules affecting transcription in Friedreich ataxia. Pharmacol Ther. 2007;116:236-48 pubmed
  23. Hart P, Lodi R, Rajagopalan B, Bradley J, Crilley J, Turner C, et al. Antioxidant treatment of patients with Friedreich ataxia: four-year follow-up. Arch Neurol. 2005;62:621-6 pubmed
    ..This therapy resulted in sustained improvement in mitochondrial energy synthesis that was associated with a slowing of the progression of certain clinical features and a significant improvement in cardiac function. ..
  24. Hebert M. Targeting the gene in Friedreich ataxia. Biochimie. 2008;90:1131-9 pubmed publisher
    ..This review will focus on the progress of potential treatment strategies for Friedreich ataxia that target the GAA expanded gene and seek to increase the level of frataxin message and protein. ..
  25. 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. ..
  26. Schagerlöf U, Elmlund H, Gakh O, Nordlund G, Hebert H, Lindahl M, et al. Structural basis of the iron storage function of frataxin from single-particle reconstruction of the iron-loaded oligomer. Biochemistry. 2008;47:4948-54 pubmed publisher
    ..These include the overall organization of the oligomers, the way they are stabilized, and the mechanisms of iron core nucleation. ..
  27. Correia A, Pastore C, Adinolfi S, Pastore A, Gomes C. Dynamics, stability and iron-binding activity of frataxin clinical mutants. FEBS J. 2008;275:3680-90 pubmed publisher
  28. Correia A, Adinolfi S, Pastore A, Gomes C. Conformational stability of human frataxin and effect of Friedreich's ataxia-related mutations on protein folding. Biochem J. 2006;398:605-11 pubmed
  29. Vazzola V, Losa A, Soave C, Murgia I. Knockout of frataxin gene causes embryo lethality in Arabidopsis. FEBS Lett. 2007;581:667-72 pubmed
  30. Pandolfo M, Pastore A. The pathogenesis of Friedreich ataxia and the structure and function of frataxin. J Neurol. 2009;256 Suppl 1:9-17 pubmed publisher
    ..To understand FRDA pathogenesis and to design novel therapeutic strategies, we must first precisely identify the cellular role of frataxin. ..
  31. He Y, Alam S, Proteasa S, Zhang Y, Lesuisse E, Dancis A, et al. Yeast frataxin solution structure, iron binding, and ferrochelatase interaction. Biochemistry. 2004;43:16254-62 pubmed
    ..NMR spectroscopy was further used to identify the intermolecular binding interface between ferrochelatase and frataxin. Ferrochelatase appears to bind to frataxin's helical plane in a manner that includes its iron-binding interface. ..
  32. 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...
  33. Kakhlon O, Manning H, Breuer W, Melamed Book N, Lu C, Cortopassi G, et al. Cell functions impaired by frataxin deficiency are restored by drug-mediated iron relocation. Blood. 2008;112:5219-27 pubmed publisher
    ..The siderophore-like properties of deferiprone provide a rational basis for treating diseases of iron misdistribution, such as FRDA, anemia of chronic disease, and X-linked sideroblastic anemia with ataxia. ..
  34. Greene E, Entezam A, Kumari D, Usdin K. Ancient repeated DNA elements and the regulation of the human frataxin promoter. Genomics. 2005;85:221-30 pubmed
  35. Wang D, Kim B, Lee K, Yoon H, Cui Z, Lu W, et al. Molecular characterization of iron binding proteins, transferrin and ferritin heavy chain subunit, from the bumblebee Bombus ignitus. Comp Biochem Physiol B Biochem Mol Biol. 2009;152:20-7 pubmed publisher
    ..ignitus worker bees revealed that Bi-Tf and Bi-FerHCH are differentially induced in a time-dependent manner in a single insect by wounding, bacterial challenge, and iron overload. ..
  36. M Rindler P, Clark R, Pollard L, De Biase I, Bidichandani S. Replication in mammalian cells recapitulates the locus-specific differences in somatic instability of genomic GAA triplet-repeats. Nucleic Acids Res. 2006;34:6352-61 pubmed
    ..These data suggest that mammalian DNA replication is a possible mechanism underlying locus-specific differences in instability of GAA triplet-repeat sequences. ..
  37. Thierbach R, Schulz T, Isken F, Voigt A, Mietzner B, Drewes G, et al. Targeted disruption of hepatic frataxin expression causes impaired mitochondrial function, decreased life span and tumor growth in mice. Hum Mol Genet. 2005;14:3857-64 pubmed
    ..Taken together, these findings indicate that frataxin may act as a mitochondrial tumor suppressor protein in mammals. ..
  38. Coppola G, Choi S, Santos M, Miranda C, Tentler D, Wexler E, et al. Gene expression profiling in frataxin deficient mice: microarray evidence for significant expression changes without detectable neurodegeneration. Neurobiol Dis. 2006;22:302-11 pubmed
    ..The identification of a core set of genes changing early in the FRDA pathogenesis can be a useful tool in both clarifying the disease process and in evaluating new therapeutic strategies...
  39. Condo I, Ventura N, Malisan F, Rufini A, Tomassini B, Testi R. In vivo maturation of human frataxin. Hum Mol Genet. 2007;16:1534-40 pubmed
  40. Burnett R, Melander C, Puckett J, Son L, Wells R, Dervan P, et al. DNA sequence-specific polyamides alleviate transcription inhibition associated with long GAA.TTC repeats in Friedreich's ataxia. Proc Natl Acad Sci U S A. 2006;103:11497-502 pubmed
    ..Polyamides may increase transcription by altering the DNA conformation of genes harboring long GAA.TTC repeats or by chromatin opening. ..
  41. Yoon T, Dizin E, Cowan J. N-terminal iron-mediated self-cleavage of human frataxin: regulation of iron binding and complex formation with target proteins. J Biol Inorg Chem. 2007;12:535-42 pubmed
    ..The physiological significance of iron-mediated release of the N-terminal residues from this anionic surface is discussed. ..
  42. Krasilnikova M, Kireeva M, Petrovic V, Knijnikova N, Kashlev M, Mirkin S. Effects of Friedreich's ataxia (GAA)n*(TTC)n repeats on RNA synthesis and stability. Nucleic Acids Res. 2007;35:1075-84 pubmed
    ..We have determined that these RNA truncations are consistent with cleavage of the full-sized mRNAs at (UUC)n runs by the E. coli degradosome. ..
  43. Foury F, Pastore A, Trincal M. Acidic residues of yeast frataxin have an essential role in Fe-S cluster assembly. EMBO Rep. 2007;8:194-9 pubmed
    ..Therefore, the acidic ridge is essential for the Yfh1 function and is likely to be involved in iron-mediated protein-protein interactions. ..
  44. Bou Abdallah F, Adinolfi S, Pastore A, Laue T, Dennis Chasteen N. Iron binding and oxidation kinetics in frataxin CyaY of Escherichia coli. J Mol Biol. 2004;341:605-15 pubmed
    ..The observed iron oxidation and binding properties of frataxin CyaY may afford the mitochondria protection against iron-induced oxidative damage. ..
  45. Schulz T, Thierbach R, Voigt A, Drewes G, Mietzner B, Steinberg P, et al. Induction of oxidative metabolism by mitochondrial frataxin inhibits cancer growth: Otto Warburg revisited. J Biol Chem. 2006;281:977-81 pubmed
    ..Taken together, these results support the view that an increase in oxidative metabolism induced by mitochondrial frataxin may inhibit cancer growth in mammals. ..
  46. Stehling O, Elsässer H, Brückel B, Muhlenhoff U, Lill R. Iron-sulfur protein maturation in human cells: evidence for a function of frataxin. Hum Mol Genet. 2004;13:3007-15 pubmed
    ..These results demonstrate (i) that frataxin is a component of the human Fe/S cluster assembly machinery and (ii) that it plays a role in the maturation of both mitochondrial and cytosolic Fe/S proteins. ..
  47. Bencze K, Kondapalli K, Cook J, McMahon S, Millán Pacheco C, Pastor N, et al. The structure and function of frataxin. Crit Rev Biochem Mol Biol. 2006;41:269-91 pubmed
    ..This review focuses on the structural and biochemical aspects of iron binding by the frataxin orthologs and outlines molecular attributes that may help explain the protein's role in different cellular pathways. ..
  48. O Neill H, Gakh O, Isaya G. Supramolecular assemblies of human frataxin are formed via subunit-subunit interactions mediated by a non-conserved amino-terminal region. J Mol Biol. 2005;345:433-9 pubmed
    ..We propose that human frataxin is a modular protein that depends on self-assembly to accomplish its diverse functions. ..
  49. Cook J, Bencze K, Jankovic A, Crater A, Busch C, Bradley P, et al. Monomeric yeast frataxin is an iron-binding protein. Biochemistry. 2006;45:7767-77 pubmed
    ..On the basis of our results, we have developed a model for how we believe yeast frataxin interacts with iron. ..
  50. Rai M, Soragni E, Jenssen K, Burnett R, Herman D, Coppola G, et al. HDAC inhibitors correct frataxin deficiency in a Friedreich ataxia mouse model. PLoS ONE. 2008;3:e1958 pubmed publisher
  51. Gakh O, Park S, Liu G, Macomber L, Imlay J, Ferreira G, et al. Mitochondrial iron detoxification is a primary function of frataxin that limits oxidative damage and preserves cell longevity. Hum Mol Genet. 2006;15:467-79 pubmed
  52. Younger J, Ren H, Chen L, Fan C, Fields A, Patterson C, et al. A foldable CFTR{Delta}F508 biogenic intermediate accumulates upon inhibition of the Hsc70-CHIP E3 ubiquitin ligase. J Cell Biol. 2004;167:1075-85 pubmed
    ..Inhibition of CFTRDeltaF508 ubiquitination can increase its cell surface expression and may provide an approach to treat CF. ..
  53. Greene E, Mahishi L, Entezam A, Kumari D, Usdin K. Repeat-induced epigenetic changes in intron 1 of the frataxin gene and its consequences in Friedreich ataxia. Nucleic Acids Res. 2007;35:3383-90 pubmed
    ..Our results also raise the possibility that the repeat-mediated increases in DNA methylation in the FXN gene in FRDA patients are secondary to the chromatin changes. ..