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Each member of the poly-r(C)-binding protein 1 (PCBP) family exhibits iron chaperone activity toward ferritin

Sebastien Leidgens1, Kimberly Z Bullough, Haifeng Shi

  • 1From the Liver Diseases Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-1800, USA.

The Journal of Biological Chemistry
|May 4, 2013
PubMed

Insights

Poly (rC)-binding proteins (PCBPs) are crucial for delivering iron to ferritin, an essential protein for iron storage. PCBP1 and PCBP2 act as iron chaperones, facilitating iron incorporation into ferritin and regulating cellular iron homeostasis.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Iron-dependent enzymes require specific metal cofactors for function.
  • Poly (rC)-binding protein 1 (PCBP1) is known as an iron chaperone for ferritin.
  • PCBP1 and its paralog PCBP2 are essential for iron delivery to prolyl hydroxylase, regulating HIF1.

Purpose of the Study:

  • To investigate the role of PCBP2 as an iron chaperone for ferritin.
  • To elucidate the interactions between Poly (rC)-binding proteins (PCBPs) and ferritin.
  • To understand the function of different PCBP family members in iron metabolism.

Main Methods:

  • Co-expression of PCBP2 and human ferritins in yeast.
  • Depletion of PCBP2 in Huh7 cells.
  • Co-immunoprecipitation assays in HEK293 cells.
  • In vitro binding assays.
  • Expression of PCBP3 and PCBP4 in yeast.

Main Results:

  • PCBP2 functions as an iron chaperone for ferritin, enhancing iron deposition.
  • PCBP1 and PCBP2 are required for ferritin complex formation and exhibit high-affinity binding to ferritin.
  • PCBP3 and PCBP4 also activate the iron deficiency response in yeast, with PCBP3 showing strong ferritin interaction.
  • PCBP1 exacerbates iron toxicity, while PCBP4 confers protection in an iron-sensitive yeast strain.

Conclusions:

  • PCBP1 and PCBP2 form a complex for iron delivery to ferritin.
  • All PCBP family members may possess iron chaperone activity, with distinct roles in iron metabolism and cellular response to iron levels.

Keywords:
IronMetalsMolecular ChaperoneRibonuclear Protein (RNP)Transport MetalsYeast MetabolismhnRNP

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