Ero1p: a novel and ubiquitous protein with an essential role in oxidative protein folding in the endoplasmic reticulum.
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.
Pollard
M G
MG
Department of Cellular and Molecular Pharmacology, University of California, San Francisco 94143-0450, USA.
Travers
K J
KJ
Weissman
J S
JS
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
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