A novel disulphide switch mechanism in Ero1 balances ER oxidation in human cells

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

A novel disulphide switch mechanism in Ero1 balances ER oxidation in human cells. / Appenzeller-Herzog, Christian; Riemer, Jan; Christensen, Brian; Sørensen, Esben B.; Ellgaard, Lars.

In: EMBO Journal, Vol. 27, 2008, p. 2977–2987.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Appenzeller-Herzog, C, Riemer, J, Christensen, B, Sørensen, EB & Ellgaard, L 2008, 'A novel disulphide switch mechanism in Ero1 balances ER oxidation in human cells', EMBO Journal, vol. 27, pp. 2977–2987. https://doi.org/10.1038/emboj.2008.202

APA

Appenzeller-Herzog, C., Riemer, J., Christensen, B., Sørensen, E. B., & Ellgaard, L. (2008). A novel disulphide switch mechanism in Ero1 balances ER oxidation in human cells. EMBO Journal, 27, 2977–2987. https://doi.org/10.1038/emboj.2008.202

Vancouver

Appenzeller-Herzog C, Riemer J, Christensen B, Sørensen EB, Ellgaard L. A novel disulphide switch mechanism in Ero1 balances ER oxidation in human cells. EMBO Journal. 2008;27:2977–2987. https://doi.org/10.1038/emboj.2008.202

Author

Appenzeller-Herzog, Christian ; Riemer, Jan ; Christensen, Brian ; Sørensen, Esben B. ; Ellgaard, Lars. / A novel disulphide switch mechanism in Ero1 balances ER oxidation in human cells. In: EMBO Journal. 2008 ; Vol. 27. pp. 2977–2987.

Bibtex

@article{6b1a6740e16211ddb5fc000ea68e967b,
title = "A novel disulphide switch mechanism in Ero1 balances ER oxidation in human cells",
abstract = "Oxidative maturation of secretory and membrane proteins in the endoplasmic reticulum (ER) is powered by Ero1 oxidases. To prevent cellular hyperoxidation, Ero1 activity can be regulated by intramolecular disulphide switches. Here, we determine the redox-driven shutdown mechanism of Ero1, the housekeeping Ero1 enzyme in human cells. We show that functional silencing of Ero1 in cells arises from the formation of a disulphide bond-identified by mass spectrometry-between the active-site Cys94 (connected to Cys99 in the active enzyme) and Cys131. Competition between substrate thiols and Cys131 creates a feedback loop where activation of Ero1 is linked to the availability of its substrate, reduced protein disulphide isomerase (PDI). Overexpression of Ero1-Cys131Ala or the isoform Ero1, which does not have an equivalent disulphide switch, leads to augmented ER oxidation. These data reveal a novel regulatory feedback system where PDI emerges as a central regulator of ER redox homoeostasis.",
author = "Christian Appenzeller-Herzog and Jan Riemer and Brian Christensen and S{\o}rensen, {Esben B.} and Lars Ellgaard",
note = "Keywords: disulphide-bond formation, endoplasmic reticulum, ER oxidoreductin 1, protein disulphide isomerase, redox homoeostasis",
year = "2008",
doi = "10.1038/emboj.2008.202",
language = "English",
volume = "27",
pages = "2977–2987",
journal = "E M B O Journal",
issn = "0261-4189",
publisher = "Wiley-Blackwell",

}

RIS

TY - JOUR

T1 - A novel disulphide switch mechanism in Ero1 balances ER oxidation in human cells

AU - Appenzeller-Herzog, Christian

AU - Riemer, Jan

AU - Christensen, Brian

AU - Sørensen, Esben B.

AU - Ellgaard, Lars

N1 - Keywords: disulphide-bond formation, endoplasmic reticulum, ER oxidoreductin 1, protein disulphide isomerase, redox homoeostasis

PY - 2008

Y1 - 2008

N2 - Oxidative maturation of secretory and membrane proteins in the endoplasmic reticulum (ER) is powered by Ero1 oxidases. To prevent cellular hyperoxidation, Ero1 activity can be regulated by intramolecular disulphide switches. Here, we determine the redox-driven shutdown mechanism of Ero1, the housekeeping Ero1 enzyme in human cells. We show that functional silencing of Ero1 in cells arises from the formation of a disulphide bond-identified by mass spectrometry-between the active-site Cys94 (connected to Cys99 in the active enzyme) and Cys131. Competition between substrate thiols and Cys131 creates a feedback loop where activation of Ero1 is linked to the availability of its substrate, reduced protein disulphide isomerase (PDI). Overexpression of Ero1-Cys131Ala or the isoform Ero1, which does not have an equivalent disulphide switch, leads to augmented ER oxidation. These data reveal a novel regulatory feedback system where PDI emerges as a central regulator of ER redox homoeostasis.

AB - Oxidative maturation of secretory and membrane proteins in the endoplasmic reticulum (ER) is powered by Ero1 oxidases. To prevent cellular hyperoxidation, Ero1 activity can be regulated by intramolecular disulphide switches. Here, we determine the redox-driven shutdown mechanism of Ero1, the housekeeping Ero1 enzyme in human cells. We show that functional silencing of Ero1 in cells arises from the formation of a disulphide bond-identified by mass spectrometry-between the active-site Cys94 (connected to Cys99 in the active enzyme) and Cys131. Competition between substrate thiols and Cys131 creates a feedback loop where activation of Ero1 is linked to the availability of its substrate, reduced protein disulphide isomerase (PDI). Overexpression of Ero1-Cys131Ala or the isoform Ero1, which does not have an equivalent disulphide switch, leads to augmented ER oxidation. These data reveal a novel regulatory feedback system where PDI emerges as a central regulator of ER redox homoeostasis.

U2 - 10.1038/emboj.2008.202

DO - 10.1038/emboj.2008.202

M3 - Journal article

C2 - 18833192

VL - 27

SP - 2977

EP - 2987

JO - E M B O Journal

JF - E M B O Journal

SN - 0261-4189

ER -

ID: 9700629