دورية أكاديمية
أعرض في EDS

Iron-dependent self-assembly of recombinant yeast frataxin: implications for Friedreich ataxia.

التفاصيل البيبلوغرافية
العنوان: Iron-dependent self-assembly of recombinant yeast frataxin: implications for Friedreich ataxia.
المؤلفون: Adamec J; Departments of Pediatric & Adolescent Medicine and Biochemistry & Molecular Biology, Mayo Clinic and Foundation, Rochester, MN, USA., Rusnak F, Owen WG, Naylor S, Benson LM, Gacy AM, Isaya G
المصدر: American journal of human genetics [Am J Hum Genet] 2000 Sep; Vol. 67 (3), pp. 549-62. Date of Electronic Publication: 2000 Aug 04.
نوع المنشور: Journal Article; Research Support, U.S. Gov't, P.H.S.
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 0370475 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0002-9297 (Print) Linking ISSN: 00029297 NLM ISO Abbreviation: Am J Hum Genet Subsets: MEDLINE
أسماء مطبوعة: Publication: 2008- : [Cambridge, MA] : Cell Press
Original Publication: Baltimore, American Society of Human Genetics.
مواضيع طبية MeSH: Iron-Binding Proteins* , Saccharomyces cerevisiae*/cytology , Saccharomyces cerevisiae*/enzymology , Saccharomyces cerevisiae*/genetics, Friedreich Ataxia/*metabolism , Iron/*pharmacology , Phosphotransferases (Alcohol Group Acceptor)/*metabolism, Chromatography, Gel ; Escherichia coli/genetics ; Friedreich Ataxia/enzymology ; Friedreich Ataxia/genetics ; Homeostasis ; Humans ; Iron/analysis ; Iron/metabolism ; Iron Chelating Agents/pharmacology ; Microscopy, Atomic Force ; Microscopy, Electron ; Mitochondria/enzymology ; Mitochondria/metabolism ; Models, Biological ; Molecular Sequence Data ; Molecular Weight ; Oxidative Stress ; Phosphotransferases (Alcohol Group Acceptor)/chemistry ; Phosphotransferases (Alcohol Group Acceptor)/genetics ; Phosphotransferases (Alcohol Group Acceptor)/isolation & purification ; Protein Binding/drug effects ; Protein Structure, Quaternary/drug effects ; Recombinant Proteins/chemistry ; Recombinant Proteins/isolation & purification ; Recombinant Proteins/metabolism ; Recombinant Proteins/ultrastructure ; Reducing Agents/pharmacology ; Solubility/drug effects ; Frataxin
مستخلص: Frataxin deficiency is the primary cause of Friedreich ataxia (FRDA), an autosomal recessive cardiodegenerative and neurodegenerative disease. Frataxin is a nuclear-encoded mitochondrial protein that is widely conserved among eukaryotes. Genetic inactivation of the yeast frataxin homologue (Yfh1p) results in mitochondrial iron accumulation and hypersensitivity to oxidative stress. Increased iron deposition and evidence of oxidative damage have also been observed in cardiac tissue and cultured fibroblasts from patients with FRDA. These findings indicate that frataxin is essential for mitochondrial iron homeostasis and protection from iron-induced formation of free radicals. The functional mechanism of frataxin, however, is still unknown. We have expressed the mature form of Yfh1p (mYfh1p) in Escherichia coli and have analyzed its function in vitro. Isolated mYfh1p is a soluble monomer (13,783 Da) that contains no iron and shows no significant tendency to self-associate. Aerobic addition of ferrous iron to mYfh1p results in assembly of regular spherical multimers with a molecular mass of approximately 1. 1 MDa (megadaltons) and a diameter of 13+/-2 nm. Each multimer consists of approximately 60 subunits and can sequester >3,000 atoms of iron. Titration of mYfh1p with increasing iron concentrations supports a stepwise mechanism of multimer assembly. Sequential addition of an iron chelator and a reducing agent results in quantitative iron release with concomitant disassembly of the multimer, indicating that mYfh1p sequesters iron in an available form. In yeast mitochondria, native mYfh1p exists as monomer and a higher-order species with a molecular weight >600,000. After addition of (55)Fe to the medium, immunoprecipitates of this species contain >16 atoms of (55)Fe per molecule of mYfh1p. We propose that iron-dependent self-assembly of recombinant mYfh1p reflects a physiological role for frataxin in mitochondrial iron sequestration and bioavailability.
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معلومات مُعتمدة: R01 AG015709 United States AG NIA NIH HHS; AG15709 United States AG NIA NIH HHS
سلسلة جزيئية: GENBANK Z74168
المشرفين على المادة: 0 (Iron Chelating Agents)
0 (Iron-Binding Proteins)
0 (Recombinant Proteins)
0 (Reducing Agents)
E1UOL152H7 (Iron)
EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
تواريخ الأحداث: Date Created: 20000810 Date Completed: 20000919 Latest Revision: 20240412
رمز التحديث: 20240412
مُعرف محوري في PubMed: PMC1287515
DOI: 10.1086/303056
PMID: 10930361
قاعدة البيانات: MEDLINE
الوصف
تدمد:0002-9297
DOI:10.1086/303056