scholarly journals μ-1,2-Peroxobridged di-iron(III) dimer formation in human H-chain ferritin

2002 ◽  
Vol 364 (1) ◽  
pp. 57-63 ◽  
Author(s):  
Fadi BOU-ABDALLAH ◽  
Georgia C. PAPAEFTHYMIOU ◽  
Danielle M. SCHESWOHL ◽  
Sean D. STANGA ◽  
Paolo AROSIO ◽  
...  
Keyword(s):  
Iron Oxidation ◽  
Iron Core ◽  
Intermediate Species ◽  
Direct Oxidation ◽  
Dimer Formation ◽  
Complex Species ◽  
Ferritin Iron ◽  
Human Ferritin ◽  
Mössbauer Parameters ◽  
Almost All

Biomineralization of the ferritin iron core involves a complex series of events in which H2O2 is produced during iron oxidation by O2 at a dinuclear centre, the ‘ferroxidase site’, located on the H-subunit of mammalian proteins. Rapid-freeze quench Mössbauer spectroscopy was used to probe the early events of iron oxidation and mineralization in recombinant human ferritin containing 24 H-subunits. The spectra reveal that a μ-1,2-peroxodiFe(III) intermediate (species P) with Mössbauer parameters δ (isomer shift) = 0.58mm/s and ΔEQ (quadrupole splitting) = 1.07mm/s at 4.2K is formed within 50ms of mixing Fe(II) with the apoprotein. This intermediate accounts for almost all of the iron in the sample at 160ms. It subsequently decays within 10s to form a μ-oxodiFe(III)—protein complex (species D), which partially vacates the ferroxidase sites of the protein to generate Fe(III) clusters (species C) at a reaction time of 10min. The intermediate peroxodiFe(III) complex does not decay under O2-limiting conditions, an observation suggesting inhibition of decay by unreacted Fe(II), or a possible role for O2 in ferritin biomineralization in addition to that of direct oxidation of iron(II).

scholarly journals Mutational analysis of the channel and loop sequences of human ferritin H-chain

1989 ◽  
Vol 264 (2) ◽  
pp. 381-388 ◽  
Author(s):  
S Levi ◽  
A Luzzago ◽  
F Franceschinelli ◽  
P Santambrogio ◽  
G Cesareni ◽  
...  
Keyword(s):  
Amino Acid ◽  
Iron Uptake ◽  
Iron Oxidation ◽  
Single Amino Acid ◽  
Iron Core ◽  
Amino Acid Residues ◽  
Terminal Sequence ◽  
Loop Sequence ◽  
Human Ferritin ◽  
Ferritin H

Human ferritin H-chain mutants were obtained by engineering the recombinant protein expressed by Escherichia coli. The mutagenesis were directed to the C-terminal sequence forming the hydrophobic channel, to the hydrophilic channel and to the loop sequence. The mutants were analysed for extent of expression, for stability, for capacity to incorporate iron and for kinetics of iron uptake and iron oxidation. Of the 22 mutants analysed only two with deletions of single residues in the loop sequence and one with deletion of the last 28 amino acid residues did not assemble into ferritin-like proteins. The other mutants assembled correctly and showed similar chemical/physical properties to the wild-type; they included duplication of an 18-amino acid-residue stretch, deletion of the last 22 and the last seven residues and various mutations of single amino acid residues. Two mutants with extensive alteration in the C-terminal sequence had a diminished thermostability associated with incapability to incorporate iron though they still catalysed iron oxidation. The mutants with alterations of the sequence around the hydrophilic channel showed diminished iron uptake and oxidation kinetics, together with a slightly larger apparent molecular size. The results indicate (i) that two of the sequences are important for ferritin assembly/stability, (ii) that the presence of the hydrophobic channel is essential for formation of the iron core and (iii) that the sites of iron interaction and the path of iron penetration into ferritin remain unidentified.

Desulfovibrio vulgaris bacterioferritin uses H2O2 as a co-substrate for iron oxidation and reveals DPS-like DNA protection and binding activities

2012 ◽  
Vol 446 (1) ◽  
pp. 125-133 ◽  
Author(s):  
Cristina G. Timóteo ◽  
Márcia Guilherme ◽  
Daniela Penas ◽  
Filipe Folgosa ◽  
Pedro Tavares ◽  
...  
Keyword(s):  
Iron Oxidation ◽  
Reaction Rates ◽  
Desulfovibrio Vulgaris ◽  
Intermediate Species ◽  
Dna Protection ◽  
Gene Encoding ◽  
H2o2 Oxidation ◽  
Mössbauer Parameters ◽  
The One

A gene encoding Bfr (bacterioferritin) was identified and isolated from the genome of Desulfovibrio vulgaris cells, and overexpressed in Escherichia coli. In vitro, H2O2 oxidizes Fe2+ ions at much higher reaction rates than O2. The H2O2 oxidation of two Fe2+ ions was proven by Mössbauer spectroscopy of rapid freeze-quenched samples. On the basis of the Mössbauer parameters of the intermediate species we propose that D. vulgaris Bfr follows a mineralization mechanism similar to the one reported for vertebrate H-type ferritins subunits, in which a diferrous centre at the ferroxidase site is oxidized to diferric intermediate species, that are subsequently translocated into the inner nanocavity. D. vulgaris recombinant Bfr oxidizes and stores up to 600 iron atoms per protein. This Bfr is able to bind DNA and protect it against hydroxyl radical and DNase deleterious effects. The use of H2O2 as an oxidant, combined with the DNA binding and protection activities, seems to indicate a DPS (DNAbinding protein from starved cells)-like role for D. vulgaris Bfr.

scholarly journals Defining the roles of the threefold channels in iron uptake, iron oxidation and iron-core formation in ferritin: a study aided by site-directed mutagenesis

1993 ◽  
Vol 296 (3) ◽  
pp. 721-728 ◽  
Author(s):  
A Treffry ◽  
E R Bauminger ◽  
D Hechel ◽  
N W Hodson ◽  
I Nowik ◽  
...  
Keyword(s):  
Iron Uptake ◽  
Iron Oxidation ◽  
Site Directed Mutagenesis ◽  
Iron Core ◽  
Directed Mutagenesis ◽  
Difference Spectroscopy ◽  
Iron Storage ◽  
Ferritin Iron ◽  
Iron Storage Protein

This paper aims to define the role of the threefold intersubunit channels in iron uptake and sequestration processes in the iron-storage protein, ferritin. Iron uptake, measured as loss of availability of Fe(II) to ferrozine (due to oxidation), has been studied in recombinant human H-chain ferritins bearing amino acid substitutions in the threefold channels or ferroxidase centres. Similar measurements with recombinant horse L-chain ferritin are compared. It is concluded that significant Fe(II) oxidation occurs only at the H-chain ferroxidase centres and not in the threefold channels, although this route is used by Fe(II) for entry. Investigations by Mössbauer and u.v.-difference spectroscopy show that part of the iron oxidized by H-chain ferritin returns to the threefold channels as Fe(III). This monomeric Fe(III) can be displaced by addition of Tb(III). Fe(III) also moves into the cavity for formation of the iron-core mineral, ferrihydrite. Iron incorporated into ferrihydrite becomes kinetically inert.

scholarly journals Ferritin iron uptake and release. Structure–function relationships

1974 ◽  
Vol 143 (2) ◽  
pp. 445-451 ◽  
Author(s):  
Pauline M. Harrison ◽  
Terence G. Hoy ◽  
Ian G. Macara ◽  
Richard J. Hoare
Keyword(s):  
Structure Function ◽  
Iron Uptake ◽  
Iron Oxidation ◽  
Direct Interaction ◽  
Experimental Results ◽  
The Other ◽  
Iron Core ◽  
Oxidation Reduction ◽  
Ferritin Iron ◽  
Uptake And Release

Iron uptake and release by ferritin molecules of different iron contents show similar profiles. These are discussed in relation to the structure of the ferritin molecule. Two models of iron uptake and release are considered. One involves iron oxidation–reduction sites on the protein. The other allows direct interaction of reagents with the iron-core crystallites. It is concluded that the second model accounts better for the experimental results presented now and in previous publications.

THE FORMATION, STRUCTURE AND DISSOLUTION OF THE FERRITIN IRON CORE STUDIED BY X-RAY ABSORPTION SPECTROSCOPY

1986 ◽  
Vol 47 (C8) ◽  
pp. C8-1155-C8-1157
Author(s):  
E. C. THEIL ◽  
D. E. SAYERS ◽  
C. Y. YANG ◽  
A. FONTAINE ◽  
E. DARTYGE
Keyword(s):  
Absorption Spectroscopy ◽  
Iron Core ◽  
X Ray ◽  
Ferritin Iron ◽  
X Ray Absorption

Idiopathic hemochromatosis: serum ferritin concentrations during therapy by phlebotomy.

1982 ◽  
Vol 28 (8) ◽  
pp. 1806-1808 ◽  
Author(s):  
P J Garry ◽  
J H Saiki
Keyword(s):  
Serum Ferritin ◽  
Iron Absorption ◽  
Binding Capacity ◽  
Hemoglobin Concentration ◽  
Total Iron ◽  
Ferritin Iron ◽  
Idiopathic Hemochromatosis ◽  
Total Body ◽  
Almost All ◽  
Iron Binding Capacity

Abstract We report the case of a 54-year-old man who presented with symptoms of idiopathic hemochromatosis, an inherited disorder involving regulation of iron absorption. These symptoms usually do not appear until total body iron content reaches 15 g, about threefold normal. Therapy involves mobilization and removal of excess stored iron through weekly or twice-weekly phlebotomies of 500 mL, until the hemoglobin concentration becomes less than 110 g/L and remains there for several weeks, or until serum ferritin concentrations indicate that almost all the stored iron has been removed (ferritin less than 12 micrograms/L). Here, concentrations of ferritin in serum were used as an index to iron overload and removal of stored iron. We report changes in hemoglobin, serum ferritin, iron, and total iron-binding capacity during the course of removing by phlebotomy more than 20 g of iron from a patient with idiopathic hemochromatosis.

A Mechanism for Ferritin-Iron Oxidation and Deposition

1977 ◽  
Vol 5 (4) ◽  
pp. 1126-1128 ◽  
Author(s):  
ROBERT R. CRICHTON ◽  
FRANÇOISE ROMAN
Keyword(s):  
Iron Oxidation ◽  
Ferritin Iron

A 7-nm nanocolumn structure fabricated by using a ferritin iron-core mask and low-energy Cl neutral beams

2004 ◽  
Vol 84 (9) ◽  
pp. 1555-1557 ◽  
Author(s):  
Tomohiro Kubota ◽  
Tomohiro Baba ◽  
Seiji Samukawa ◽  
Hiroyuki Kawashima ◽  
Yukiharu Uraoka ◽  
...  
Keyword(s):  
Low Energy ◽  
Iron Core ◽  
Neutral Beams ◽  
Ferritin Iron

scholarly journals Cryo-EM Structure of Bacterioferritin Nanocages Provides Insight into the Bio-mineralization of Ferritins

2021 ◽  
Author(s):  
Chacko Jobichen ◽  
Tan Ying Chong ◽  
Rajesh Rattinam ◽  
Sandip Basak ◽  
Mahalashmi Srinivasan ◽  
...  
Keyword(s):  
Iron Transport ◽  
Streptomyces Coelicolor ◽  
Iron Oxidation ◽  
Essential Element ◽  
Wild Type ◽  
Complete Structure ◽  
Iron Trafficking ◽  
Human Ferritin ◽  
Protein Shell ◽  
Insight Into

AbstractIron is an essential element involved in various metabolic processes. The ferritin family of proteins forms nanocage assembly and are involved in iron oxidation, storage and mineralization. Although several structures of human ferritin and bacterioferritin subunits have been resolved, there is still no complete structure that shows both the trapped Fe-biomineral cluster along with the nanocage. Furthermore, whereas the mechanism of iron trafficking has been explained using various approaches, an atomic-level description of the pathway and the biomineralization that occurs inside the cavity are lacking. Here, we report three cryo-EM structures of different states of the Streptomyces coelicolor bacterioferritin nanocage (i.e., apo, holo) at 3.4 Å to 4.6 Å resolution and the subunit crystal structure at 2.6 Å resolution. The holo forms show different stages of Fe-biomineral accumulation inside the nanocage and suggest the possibility of a different Fe biomineral accumulation process. The cryo-EM map shows connections between the Fe-biomineral cluster and residues such as Thr157 and Lys42 from the protein shell, which are involved in iron transport. Mutation and truncation of the bacterioferritin residues involved in these connections can significantly reduce iron binding as compared with wild type bacterioferritin. Moreover, S. coelicolor bacterioferritin binds to various DNA fragments, similar to Dps (DNA-binding protein from starved cells) proteins. Collectively, our results represent a prototype for the ferritin nanocage, revealing insight into its biomineralization and the potential channel for ferritin-associated iron trafficking.

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