The endoplasmic reticulum sulfhydryl oxidase Ero1β drives efficient oxidative protein folding with loose regulation

Biochem J. 2011 Feb 15;434(1):113-21. doi: 10.1042/BJ20101357.

Abstract

In eukaryotes, disulfide bonds are formed in the endoplasmic reticulum, facilitated by the Ero1 (endoplasmic reticulum oxidoreductin 1) oxidase/PDI (protein disulfide-isomerase) system. Mammals have two ERO1 genes, encoding Ero1α and Ero1β proteins. Ero1β is constitutively expressed in professional secretory tissues and induced during the unfolded protein response. In the present work, we show that recombinant human Ero1β is twice as active as Ero1α in enzymatic assays. Ero1β oxidizes PDI more efficiently than other PDI family members and drives oxidative protein folding preferentially via the active site in the á domain of PDI. Our results reveal that Ero1β oxidase activity is regulated by long-range disulfide bonds and that Cys130 plays a critical role in feedback regulation. Compared with Ero1α, however, Ero1β is loosely regulated, consistent with its role as a more active oxidase when massive oxidative power is required.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Disulfides
  • Endoplasmic Reticulum / enzymology*
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Oxidation-Reduction
  • Oxidoreductases Acting on Sulfur Group Donors / genetics
  • Oxidoreductases Acting on Sulfur Group Donors / metabolism*
  • Oxygen Consumption
  • Protein Disulfide-Isomerases / genetics
  • Protein Disulfide-Isomerases / metabolism
  • Protein Folding
  • Recombinant Proteins

Substances

  • Disulfides
  • Membrane Glycoproteins
  • Recombinant Proteins
  • Oxidoreductases Acting on Sulfur Group Donors
  • ERO1B protein, human
  • Protein Disulfide-Isomerases