Ero1p: a novel and ubiquitous protein with an essential role in oxidative protein folding in the endoplasmic reticulum

Mol Cell. 1998 Jan;1(2):171-82. doi: 10.1016/s1097-2765(00)80018-0.

Abstract

The structure of many proteins entering the secretory pathway is dependent on stabilization by disulfide bonds. To support disulfide-linked folding, the endoplasmic reticulum (ER) must maintain a strongly oxidizing environment compared to the highly reduced environment of the cytosol. We report here the identification and characterization of Ero1p, a novel and essential ER-resident protein. Mutations in Ero1p cause extreme sensitivity to the reducing agent DTT, whereas overexpression confers DTT resistance. Strikingly, compromised Ero1p function results in ER retention of disulfide-stabilized proteins in a reduced, nonnative form, while not affecting structural maturation of a disulfide-free protein. We conclude that there exists a specific cellular redox machinery required for disulfide-linked protein folding in the ER and that Ero1p is an essential component of this machinery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Conserved Sequence
  • Disulfides / metabolism
  • Dithiothreitol / analogs & derivatives
  • Dithiothreitol / pharmacology
  • Endoplasmic Reticulum / chemistry*
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / enzymology
  • Flow Cytometry
  • Fungal Proteins / chemistry
  • Fungal Proteins / metabolism*
  • Gene Expression Regulation, Fungal / physiology
  • Glycoproteins / chemistry
  • Glycoproteins / genetics*
  • Glycoproteins / metabolism
  • Glycoside Hydrolases / chemistry
  • Glycoside Hydrolases / metabolism
  • Humans
  • Male
  • Membrane Glycoproteins*
  • Molecular Sequence Data
  • Mutagenesis / physiology
  • Oxidation-Reduction
  • Oxidoreductases
  • Oxidoreductases Acting on Sulfur Group Donors
  • Protein Folding
  • Saccharomyces cerevisiae / chemistry*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins*
  • Sequence Homology, Amino Acid
  • beta-Fructofuranosidase

Substances

  • Antioxidants
  • Disulfides
  • Fungal Proteins
  • Glycoproteins
  • Membrane Glycoproteins
  • Saccharomyces cerevisiae Proteins
  • dithiothreitol tetraacetate
  • ERO1A protein, human
  • Oxidoreductases
  • Oxidoreductases Acting on Sulfur Group Donors
  • ERO1 protein, S cerevisiae
  • Glycoside Hydrolases
  • beta-Fructofuranosidase
  • Dithiothreitol