Iron uptake in ferritin is blocked by binding of [Cr(TREN)(H
 2
 O)(OH)]
 2+
 , a slow dissociating model for [Fe(H
 2
 O)
 6
 ]
 2+

Barnes, Carmen; Theil, Elizabeth C.; Raymond, Kenneth N.

doi:10.1073/pnas.032089399

Cited by 33 publications

(24 citation statements)

References 54 publications

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“…B, Rate sensitivity when the C/D loop is manipulated at ion pair arginine 72 and aspartate 122, and by increasing the C/D loop size by inserting a second set of the same loop amino acids, with all the wild type gating residues present. Data from reference [9]. Temperature effects on global structure were measured at 280 nm (UV absorbance) and on pore structure at 280 nm (circular dichroism), as described in reference [3], using recombinant, mineralized ferritins in 0.015M MOPS, pH = 7.…”

Section: Summary and Perspectivementioning

confidence: 99%

“…Current models of ferrous ion entry through the gated pores into the nanocage are based on competition with other metal ions [4][5][6][7][8][9], mutagenesis of non-gating residues around the pore [8,10], and co-crystal structures with metal inhibitors [11]. The model is weakened by the absence of crystal structures of the mutant proteins, by the multiple sites for metal inhibitor binding in addition to the pores, and by studies suggesting other ferrous ion entry sites besides the gated pores [12,13].…”

Section: Introductionmentioning

confidence: 99%

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Gated pores in the ferritin protein nanocage

Theil

Liu

Tosha

2008

Inorganica Chimica Acta

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Synopsis and pictogram: Gated pores in the ferritin family of protein nanocages, illustrated in the pictogram, control transfer of ferrous iron into and out of the cages by regulating contact between hydrated ferric oxide mineral inside the protein cage, and reductants such as FMNH 2 on the outside. The structural and functional homology between the gated ion channel proteins in inaccessible membranes and gated ferritin pores in the stable, water soluble nanoprotein, make studies of ferritin pores models for gated pores in many ion channel proteins.Properties of ferritin gated pores, which control rates of FMNH 2 reduction of ferric iron in hydrated oxide minerals inside the protein nanocage, are discussed in terms of the conserved pore gate residues (arginine 72-apspartate 122 and leucine 110-leucine 134), of pore sensitivity to heat at temperatures 30 °C below that of the nanocage itself, and of pore sensitivity to physiological changes in urea (1-10 mM). Conditions which alter ferritin pore structure/function in solution, coupled with the high evolutionary conservation of the pore gates, suggest the presence of molecular regulators in vivo that recognize the pore gates and hold them either closed or open, depending on biological iron need. The apparent homology between ferrous ion transport through gated pores in the ferritin nanocage and ion transport through gated pores in ion channel proteins embedded in cell membranes, make studies of water soluble ferritin and the pore gating folding/unfolding a useful model for other gated pores.

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Section: Summary and Perspectivementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Gated pores in the ferritin protein nanocage

Theil

Liu

Tosha

2008

Inorganica Chimica Acta

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“…The diameter of fully hydrated Fe 2+ ions is 6.9 Å suggesting that in order for Fe 2+ to pass through ferritin ion channels, either partial/full dehydration of Fe 2+ •(H 2 O) 6 , protein channel conformational flexing/channel widening, or both is required, in order for the Fe 2+ substrate to reach the enzyme sites in ferritin [24]. Variable-temperature variable field (VTVH) magnetic circular dichroism (MCD) spectroscopy of Fe 2+ ions bound to ferritin enzymatic sites demonstrated that Fe 2+ in this environment is coordinated by only a single water molecule.…”

Section: Introductionmentioning

confidence: 99%

Fe2+ substrate transport through ferritin protein cage ion channels influences enzyme activity and biomineralization

et al. 2015

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Ferritins, complex protein nanocages, form internal iron-oxy minerals (Fe2O3.H2O), by moving cytoplasmic Fe2+ through intracage ion channels to cage-embedded enzyme (2Fe2+/O2 oxidoreductase) sites where ferritin biomineralization is initiated. The products of ferritin enzyme activity are diferric oxy complexes that are mineral precursors. Conserved, carboxylate amino acid side chains of D127 from each of three cage subunits project into ferritin ion channels near the interior ion channel exits and, thus, could direct Fe2+ movement to the internal enzyme sites. Ferritin D127E was designed and analyzed to probe properties of ion channel size and carboxylate crowding near the internal ion channel opening. Glu side chains are chemically equivalent to, but longer by one – CH2 than Asp, side chains. Ferritin D127E assembled into normal protein cages, but diferric peroxo formation (enzyme activity) was not observed, when measured at 650nm (DFP λmax). The caged biomineral formation, measured at 350 nm in the middle of the broad, nonspecific Fe3+-O absorption band, was slower. Structural differences (protein X-ray crystallography), between ion channels in wild type and ferritin D127E, which correlate with the inhibition of ferritin D127E enzyme activity include: 1. narrower interior ion channel openings/pores, 2. increased numbers of ion channel protein-metal binding sites, and 3. a change in ion channel electrostatics due to carboxylate crowding. The contributions of ion channel size and structure to ferritin activity reflect metal ion transport in ion channels are precisely regulated both in ferritin protein nanocages and membranes of living cells.

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“…13 Chromium has been found to compete with Fe for binding to transferrin and impairs Fe metabolism and storage; in animals, the reduced Fe, Fe binding capacity, and ferritin correlated with reduced hemoglobin. 14,15 However, in children receiving parenteral nutrition, although elevated serum Cr was shown to correlate inversely with serum Fe, hemoglobin values did not diminish. 16 We are aware of a single animal study that found anemia that ameliorated with time with exposure to Cr.…”

Section: Discussionmentioning

confidence: 97%

An Investigation of Aircraft Worker Anemia

Muller

Allstadt²,

Rennix³

et al. 2011

Journal of Occupational &Amp; Environmental Medicine

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Anemia may be more prevalent in middle-aged workers than expected. Modern laboratories generally report a calculated hematocrit value, and using hemoglobin for most classification purposes is preferred. Characteristics of a specific workforce, including age, health, hobbies, and diet, should be taken into account when interpreting medical surveillance program findings. The value of a team approach in addressing occupational health problems was demonstrated.

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Iron uptake in ferritin is blocked by binding of [Cr(TREN)(H ₂ O)(OH)] ²⁺ , a slow dissociating model for [Fe(H ₂ O) ₆ ] ²⁺

Abstract: Ferritin concentrates iron as a hydrous ferric oxide in a protein cavity (8 nm in diameter) by using eight pores along the threefold symmetry axes of the octahedral supramolecular structure.

Cited by 33 publications

References 54 publications

Gated pores in the ferritin protein nanocage

Gated pores in the ferritin protein nanocage

Fe2+ substrate transport through ferritin protein cage ion channels influences enzyme activity and biomineralization

An Investigation of Aircraft Worker Anemia

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Iron uptake in ferritin is blocked by binding of [Cr(TREN)(H 2 O)(OH)] 2+ , a slow dissociating model for [Fe(H 2 O) 6 ] 2+

Abstract: Ferritin concentrates iron as a hydrous ferric oxide in a protein cavity (8 nm in diameter) by using eight pores along the threefold symmetry axes of the octahedral supramolecular structure.

Cited by 33 publications

References 54 publications

Gated pores in the ferritin protein nanocage

Gated pores in the ferritin protein nanocage

Fe2+ substrate transport through ferritin protein cage ion channels influences enzyme activity and biomineralization

An Investigation of Aircraft Worker Anemia

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Iron uptake in ferritin is blocked by binding of [Cr(TREN)(H ₂ O)(OH)] ²⁺ , a slow dissociating model for [Fe(H ₂ O) ₆ ] ²⁺