The functional duality of iron regulatory protein 1

Curr Opin Struct Biol. 2008 Feb;18(1):106-11. doi: 10.1016/j.sbi.2007.12.010. Epub 2008 Feb 7.

Abstract

Iron homeostasis in animal cells is controlled post-transcriptionally by the iron regulatory proteins IRP1 and IRP2. IRP1 can assume two different functions in the cell, depending on conditions. During iron scarcity or oxidative stress, IRP1 binds to mRNA stem-loop structures called iron responsive elements (IREs) to modulate the translation of iron metabolism genes. In iron-rich conditions, IRP1 binds an iron-sulfur cluster to function as a cytosolic aconitase. This functional duality of IRP1 connects the translational control of iron metabolizing proteins to cellular iron levels. The recently determined structures of IRP1 in both functional states reveal the large-scale conformational changes required for these mutually exclusive roles, providing new insights into the mechanisms of IRP1 interconversion and ligand binding.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Aconitate Hydratase / chemistry
  • Aconitate Hydratase / metabolism
  • Animals
  • Base Sequence
  • Binding Sites
  • Humans
  • Iron / metabolism*
  • Iron Regulatory Protein 1 / chemistry*
  • Iron Regulatory Protein 1 / metabolism*
  • Models, Biological
  • Models, Molecular
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Protein Conformation
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / metabolism

Substances

  • RNA-Binding Proteins
  • Iron
  • Aconitate Hydratase
  • Iron Regulatory Protein 1