title: Ero1p: a novel and ubiquitous protein with an essential role in oxidative protein folding in the endoplasmic reticulum.
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.
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco 94143-0450, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Pollard
authors.forename: K J
authors.initials: KJ
authors.lastname: Travers
authors.forename: J S
authors.initials: JS
authors.lastname: Weissman
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017124:Conserved Sequence; D004220:Disulfides / Q000378:metabolism; D004229:Dithiothreitol / Q000031:analogs & derivatives / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000737:chemistry* / Q000187:drug effects / Q000201:enzymology; D005434:Flow Cytometry; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000502:physiology; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000502:physiology; D010084:Oxidation-Reduction; D010088:Oxidoreductases; D050862:Oxidoreductases Acting on Sulfur Group Donors; D017510:Protein Folding; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D043324:beta-Fructofuranosidase
chemical_list: D000975:Antioxidants; D004220:Disulfides; D005656:Fungal Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D029701:Saccharomyces cerevisiae Proteins; C085285:dithiothreitol tetraacetate; C405327:ERO1A protein, human; D010088:Oxidoreductases; D050862:Oxidoreductases Acting on Sulfur Group Donors; C113186:ERO1 protein, S cerevisiae; D006026:Glycoside Hydrolases; D043324:beta-Fructofuranosidase; D004229:Dithiothreitol