The copper-iron connection in biology

Structure of the metallo-oxidase Fet3p

Alexander B. Taylor, Christopher S. Stoj, Lynn Ziegler, Daniel J. Kosman, P. John Hart

Research output: Contribution to journalArticle

143 Citations (Scopus)

Abstract

Fet3p is a multicopper-containing glycoprotein localized to the yeast plasma membrane that catalyzes the oxidation of Fe(II) to Fe(III). This ferrous iron oxidation is coupled to the reduction of O2 to H2O and is termed the ferroxidase reaction. Fet3p-produced Fe(III) is transferred to the permease Ftr1p for import into the cytosol. The posttranslational insertion of four copper ions into Fet3p is essential for its activity, thus linking copper and iron homeostasis. The mammalian ferroxidases ceruloplasmin and hephaestin are homologs of Fet3p. Loss of the Fe(II) oxidation catalyzed by these proteins results in a spectrum of pathological states, including death. Here, we present the structure of the Fet3p extracellular ferroxidase domain and compare it with that of human ceruloplasmin and other multicopper oxidases that are devoid of ferroxidase activity. The Fet3p structure delineates features that underlie the unique reactivity of this and homologous multicopper oxidases that support the essential trafficking of iron in diverse eukaryotic organisms. The findings are correlated with biochemical and physiological data to cross-validate the elements of Fet3p that define it as both a ferroxidase and cuprous oxidase.

Original languageEnglish (US)
Pages (from-to)15459-15464
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number43
DOIs
StatePublished - Oct 25 2005

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Ceruloplasmin
Copper
Oxidoreductases
Iron
Membrane Transport Proteins
Cytosol
Glycoproteins
Homeostasis
Yeasts
Cell Membrane
Ions
Proteins

Keywords

  • Ferroxidase
  • Iron trafficking
  • Metal homeostasis
  • Multicopper oxidase

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

The copper-iron connection in biology : Structure of the metallo-oxidase Fet3p. / Taylor, Alexander B.; Stoj, Christopher S.; Ziegler, Lynn; Kosman, Daniel J.; Hart, P. John.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 43, 25.10.2005, p. 15459-15464.

Research output: Contribution to journalArticle

Taylor, Alexander B. ; Stoj, Christopher S. ; Ziegler, Lynn ; Kosman, Daniel J. ; Hart, P. John. / The copper-iron connection in biology : Structure of the metallo-oxidase Fet3p. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 43. pp. 15459-15464.
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