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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interactions of horse spleen ferritin and its derivative apoferritin with H+ ions were studied by potentiometric and spectrophotometric titration; to aid in data analysis, heats of ionization over a limited pH range and amide content were also determined. Per apoferritin subunit, all tyrosine and cysteine side chains, two of the nine lysine side chains and at least three of the six histidine side chains were found not to titrate; a preliminary but self-consistent analysis of the titration data is proposed. The titration curve of ferritin was identical with that of apoferritin in the pH range 5.5 to 3. In addition, under the conditions used, the reactivities of ferritin histidines to bromoacetate and of ferritin lysines to formaldehyde were identical with those in apoferritin. Above pH 8, a time-dependent titration of the ferritin core occurs which prevents comparison of the titration curves of the two proteins in this region. However, in the pH regions 5.5 to 7.5, two extra groups per subunit titrate reversibly in ferritin relative to apoferritin. Moreover, although the isoionic points of ferritin and apoferritin are identical in water, the isoionic point of ferritin is 0.5 pH unit lower than that of apoferritin in 0.16 to 1 M KCl. The different effects of KCl and NaCl on the two proteins indicate the presence of cation binding sites in ferritin that are absent in apoferritin and possibly also the presence of anion binding sites in apoferritin that are occupied in ferritin by anions of the core. The difference between the isoionic points of the two proteins in KCl has been interpreted to indicate the presence of approximately 2 phosphate residues per ferritin subunit which serve as cation binding sites and which are negatively charged at the isoionic point in KCl. These phosphates may also represent the additional residues that titrate in ferritin between pH 5.5 and 7.5, or may interact with positively charged residues on the inner surface of the ferritin shell, or both.
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PMID:Hydrogen ion interactions of horse spleen ferritin and apoferritin. 1 Dec 12

In apoferritin, but not in ferritin, 1.0 +/- 0.1 cysteine residue per subunit can be modified. In ferritin 3.3 +/- 0.3 lysine residues and 7.1 +/- 0.7 carboxyl groups per subunit can be modified, whilst the corresponding values for apoferritin are 4.4 +/- 0.4 lysine residues and 11.0 +/- 0.4 carboxyl groups per subunit. Modification of lysine residues which maleic anhydride and carboxyl groups with glycineamide in apoferritin which has been dissociated and denatured in guanidine hydrochloride leads to the introduction of 9.1 +/- 0.5 maleyl groups per subunit and 22.0 +/- 0.9 glycineamide residues per subunit. Whereas unmodified apoferritin subunit can be reassociated from guanidine hydrochloride to apoferritin monomer, the ability of maleylated apoferritin to reassociate is impaired. Apoferritin in which all the carboxyl groups have been blocked with glycineamide cannot be reassociated to apoferritin and exists in solution as stable subunits. The modification of one cysteine residue per subunit, of 3 or 4 lysine residues per subunit or of 7 carboxyl groups per subunit has no effect on the catalytic activity of apoferritin. In contrast the modification of 11 carboxyl groups per subunit completely abolishes the catalytic properties of the protein. We conclude that one or more carboxyl groups are essential for the catalytic activity of horse spleen apoferritin.
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PMID:Chemical modification as a probe of the topography and reactivity of horse-spleen apoferritin. 124 72

The iron-responsive element-binding protein (IRE-BP) is an RNA-binding protein that regulates the expression of several mRNAs in response to availability of cellular iron. The iron-dependent control of IRE-BP activity has been reconstituted in vitro. Incubation of purified IRE-BP with iron salts in the presence of the reducing agent cysteine decreases IRE-BP binding to the cognate RNA element. The specificity of this effect is established by several parameters: (i) the interaction of the spliceosomal protein U1A with its U1 small nuclear RNA target sequence as an internal control is unaffected by iron perturbations, (ii) non-iron metals fail to mimic the iron effect, and (iii) iron chelator activates the IRE-binding activity of IRE-BP and titrates the effect of iron salts. Modulation of IRE-BP activity by chelatable iron is reversible and thus does not involve permanent alterations of the integrity of the protein. These findings accurately mirror the physiological basis for iron regulation of transferrin receptor mRNA stability as well as ferritin and erythroid 5-aminolevulinate synthase mRNA translation in vivo. We discuss these data vis-a-vis the structural homology of IRE-BP with the iron-sulfur protein aconitase and propose a mechanism by which the same cytoplasmic protein serves a dual function as an RNA-binding factor and an enzyme.
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PMID:Modulation of the RNA-binding activity of a regulatory protein by iron in vitro: switching between enzymatic and genetic function? 158 91

A method for the purification of ferritin from rainbow trout liver by heat extraction and gel filtration is described. The number of iron atoms varied from 500 to 2000 in purified ferritin. The neutral sugar composition detected was 86 mol of glucose, 24 mol of fucose, 12 mol of galactose, and 8 mol of mannose per mol of ferritin and apoferritin. Release of iron was achieved using low molecular weight chelating agents. The order of effectiveness of chelators was nitrilotriacetate greater than EDTA greater than citrate. Removal of the iron does not imply reduction of Fe3+. The rate of release of iron increased with decreasing pH. The slowest release was at pH 7.5. The endogenous chelator is not only sulphydrylic but seems to include carbohydrates that participate in the binding of Fe2+. Trout ferritin exhibits heterogeneity upon isoelectric focusing; four isoferritins with pI values of 4.5 to 4.85 were detected. This heterogeneity represents polymorphic, not polymer, forms. The amino acid composition differs from that of ferritins from other species. High concentrations of glutamic and aspartic acids, alanine, leucine, glycine, and lysine were detected along with low concentrations of methionine and cysteine.
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PMID:Isolation and characterization of ferritin from the liver of the rainbow trout (Salmo gairdneri R.). 179 41

When assayed in vitro, the activity of the photosynthetic enzyme ribulose 1,5 bisphosphate carboxylase oxygenase is both enhanced and protected from spontaneous decay by exogenous proteins such as hemoglobin, serum albumin, and aldolase. Other proteins and amino acids tested are either ineffective (lysozyme, ferritin, lysine, and cysteine) or afford only partial protection (catalase, glycine, and phenylalanine). Protective proteins do not bind to, or exchange disulfides with, ribulose 1.5 bisphosphate carboxylase/oxygenase. Since their effect can be mimicked by reductively treated detergents such as Triton X-100, it appears that proteins protect from decay by quenching the spontaneous oxidative degradation and inhibiting surface adsorption which could lead to enzyme unfolding. Release of adsorbed molecules from the container surface is likely to be the cause of carboxylase activity enhancement.
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PMID:Protection and enhancement of ribulose 1,5 bisphosphate carboxylase activity by exogenous proteins. 191 Apr 60

Iron-responsive elements (IREs) are stemloop structures found in the mRNAs encoding ferritin and the transferrin receptor. These elements participate in the iron-induced regulation of the translation of ferritin and the stability of the transferrin receptor mRNA. Regulation in both instances is mediated by binding of a cytosolic protein to the IREs. High-affinity binding is seen when cells are starved of iron and results in repression of ferritin translation and inhibition of transferrin receptor mRNA degradation. The IRE-binding protein (IRE-BP) has been identified as an approximately 90-kDa protein that has been purified by both affinity and conventional chromatography. In this report we use RNA affinity chromatography and two-dimensional gel electrophoresis to isolate the IRE-BP for protein sequencing. A degenerate oligonucleotide probe derived from a single peptide sequence was used to isolate a cDNA clone that encodes a protein containing 13 other sequenced peptides obtained from the IRE-BP. Consistent with previous characterization of the IRE-BP, the cDNA encodes a protein of 87 kDa with a slightly acidic pI, and the corresponding mRNA of approximately 3.6 kilobases is found in a variety of cell types. The encoded protein contains a nucleotide-binding consensus sequence and regions of cysteine and histidine clusters. This mRNA is encoded by a single gene on human chromosome 9, a finding consistent with previous localization by functional mapping. The protein contains no previously defined consensus motifs for either RNA or DNA binding. The simultaneous cloning of a different, but highly homologous, cDNA suggests that the IRE-BP is a member of a distinct gene family.
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PMID:Cloning of the cDNA encoding an RNA regulatory protein--the human iron-responsive element-binding protein. 217 68

The primary structure of artemin, a major protein isolated from Artemia cysts, has been determined by direct Edman degradation of the purified protein. The amino-terminal acetylated protein has 229 amino acid residues and a high content of histidine and cysteine/cystine. A search in the GenBank Data Base at Los Alamos, using the FASTA program [Pearson, W. R. & Lipman, D. J. (1988) Proc. Natl. Acad. Sci. USA 85, 2444-2448] revealed a limited but unmistakable similarity to ferritin from vertebrates.
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PMID:The primary structure of artemin from Artemia cysts. 224 91

The knowledge of the route through which iron can enter and leave the apoferritin shell is a prerequisite for the understanding of ferritin's function. The involvement of the hydrophilic 3-fold channels in the iron uptake process has been studied by taking advantage of the reactivity of specific residues that line such channels, i.e., glutamic acid-127 and aspartic acid-130, the major Cd(II) binding sites, and cysteine-126. 113Cd NMR experiments have provided direct evidence for the competition between Fe(II) and Cd(II) binding to major Cd(II) binding sites on the protein and or a higher affinity of Fe(II) for these sites, in line with the well-known inhibitory effect of Cd(II) on iron uptake. Further evidence for the use of the 3-fold channels in the iron entry process has been obtained by means of chemical modification of Cys-126 with different mercurials. In particular, the introduction of the additional carboxylate carried by p-(chloromercuri)benzoate near Asp-127 and Glu-130 increases the initial rate of iron uptake and affects the coordination geometry of the metal in the Fe(III)-apoferritin complex as indicated by optical absorption and EPR data. The assignment of these effects to the carboxylate moiety of p-(chloromercuri)benzoate is brought out by the observation that the introduction in the 3-fold channel of the benzene ring only by means of phenylmercuric acetate has no effect on the initial iron uptake kinetics and on the spectroscopic properties of the Fe(III)-apoferritin complex.
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PMID:Identification of the iron entry channels in apoferritin. Chemical modification and spectroscopic studies. 253 62

Ferritin iron release, a process of considerable interest in biology and medicine, occurs most readily in the presence of reducing agents. Here is described a kinetic assay for measuring the rate of ferritin iron removal promoted by various reductants. The new procedure uses ferrozine as a chromophoric, high-affinity chelator for the product, Fe(II). The initial rate of iron release is quantified by continuous spectrophotometric measurement of the Fe(ferrozine)2/3+ complex which absorbs maximally at 562 nm. The initial rate of iron mobilization is dependent on reductant concentration, but not on the concentration of the chelating agent, ferrozine. Saturation kinetics are observed for all reductants, including dihydroxyfumarate, cysteine, caffeic acid, ascorbate, and glutathione. Superoxide dismutase greatly inhibits ferritin iron release by ascorbate, but has little or no effect on the reducing action of dihydroxyfumarate, cysteine, caffeic acid, or glutathione. Ferritin iron removal by dihydroxyfumarate was inhibited by various metal ions. This new assay may be used for rapid screening of test compounds for treatment of iron overload and for investigation of the mechanistic aspects of ferritin iron reduction.
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PMID:Reductive release of ferritin iron: a kinetic assay. 321 30

Ferritin-Fe(III) was rapidly and quantitatively reduced and liberated as Fe(II) by FMNH(2), FADH(2) and reduced riboflavin. Dithionite also released Fe(II) from ferritin but at less than 1% of the rate with FMNH(2). Cysteine, glutathione and ascorbate gave a similar slower rate and yielded less than 20% of the total iron from ferritin within a few hours. The reduction of ferritin-Fe(III) by the three riboflavin compounds gave complex second-order kinetics with overlapping fast and slow reactions. The fast reaction appeared to be non-specific and may be due to a reduction of Fe(III) of a lower degree of polymerization, equilibrated with ferritin iron. The amount of this Fe(3+) ion initially reduced was small, less than 0.3% of the total iron. Addition of FMN to the ferritin-dithionite system enhanced the reduction; this is due to the reduction of FMN by dithionite to form FMNH(2) which then reduces ferritin-Fe(III). A comparison of the thermodynamic parameters of FMNH(2)-ferritin and dithionite-ferritin complex formation showed that FMNH(2) required a lower activation energy and a negative entropy change, whereas dithionite required 50% more activation energy and showed a positive entropy change in ferritin reduction. The effectiveness of FMNH(2) in ferritin-Fe(III) reduction may be due to a specific binding of the riboflavin moiety to the protein portion of the ferritin molecule.
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PMID:The release of iron from horse spleen ferritin by reduced flavins. 446 57


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