ERO1-L, a human protein that favors disulfide bond formation in the endoplasmic reticulum

Andrea Cabibbo, Massimiliano Pagani, Marco Fabbri, Mariano Rocchi, Mark R. Farmery, Neil J. Bulleid, Roberto Sitia

Research output: Contribution to journalArticle

220 Citations (Scopus)

Abstract

Oxidizing conditions must be maintained in the endoplasmic reticulum (ER) to allow the formation of disulfide bonds in secretory proteins. Here we report the cloning and characterization of a mammalian gene (ERO1-L) that shares extensive homology with the Saccharomyces cerevisiae ERO1 gene, required in yeast for oxidative protein folding. When expressed in mammalian cells, the product of the human ERO1-L gene colocalizes with ER markers and displays Endo-H-sensitive glycans. In isolated microsomes, ERO1-L behaves as a type II integral membrane protein. ERO1-L is able to complement several phenotypic traits of the yeast thermosensitive mutant ero1-1, including temperature and dithiothreitol sensitivity, and intrachain disulfide bond formation in carboxypeptidase Y. ERO1-L is no longer functional when either one of the highly conserved Cys-394 or Cys-397 is mutated. These results strongly suggest that ERO1-L is involved in oxidative ER protein folding in mammalian cells.

Original languageEnglish
Pages (from-to)4827-4833
Number of pages7
JournalJournal of Biological Chemistry
Volume275
Issue number7
DOIs
Publication statusPublished - Feb 18 2000

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Endoplasmic Reticulum
Disulfides
Yeast
Protein folding
Genes
Protein Folding
Cells
Cathepsin A
Proteins
Fungal Proteins
Cloning
Dithiothreitol
Microsomes
Polysaccharides
Saccharomyces cerevisiae
Organism Cloning
Membrane Proteins
Yeasts
Display devices
Temperature

ASJC Scopus subject areas

  • Biochemistry

Cite this

ERO1-L, a human protein that favors disulfide bond formation in the endoplasmic reticulum. / Cabibbo, Andrea; Pagani, Massimiliano; Fabbri, Marco; Rocchi, Mariano; Farmery, Mark R.; Bulleid, Neil J.; Sitia, Roberto.

In: Journal of Biological Chemistry, Vol. 275, No. 7, 18.02.2000, p. 4827-4833.

Research output: Contribution to journalArticle

Cabibbo, A, Pagani, M, Fabbri, M, Rocchi, M, Farmery, MR, Bulleid, NJ & Sitia, R 2000, 'ERO1-L, a human protein that favors disulfide bond formation in the endoplasmic reticulum', Journal of Biological Chemistry, vol. 275, no. 7, pp. 4827-4833. https://doi.org/10.1074/jbc.275.7.4827
Cabibbo, Andrea ; Pagani, Massimiliano ; Fabbri, Marco ; Rocchi, Mariano ; Farmery, Mark R. ; Bulleid, Neil J. ; Sitia, Roberto. / ERO1-L, a human protein that favors disulfide bond formation in the endoplasmic reticulum. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 7. pp. 4827-4833.
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