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...

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Bibliographic Details
Published in:Molecular cell 1998, Vol.1 (2), p.171-182
Main Authors: Pollard, Michael G., Travers, Kevin J., Weissman, Jonathan S.
Format: Article
Language:English
Subjects:
Animals
Antioxidants - pharmacology
beta-Fructofuranosidase
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
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Summary: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.
ISSN:1097-2765
1097-4164
DOI:10.1016/S1097-2765(00)80018-0