The FAD- and O2-dependent reaction cycle of Ero1-mediated oxidative protein folding in the endoplasmic reticulum

Benjamin P. Tu; Jonathan S. Weissman

doi:10.1016/S1097-2765(02)00696-2

The FAD- and O₂-dependent reaction cycle of Ero1-mediated oxidative protein folding in the endoplasmic reticulum

Benjamin P. Tu, Jonathan S. Weissman

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361 Scopus citations

Abstract

The endoplasmic reticulum (ER) supports disulfide formation through an essential protein relay involving Ero1p and protein disulfide isomerase (PDI). We find that in addition to having a tightly associated flavin adenine dinucleotide (FAD) moiety, yeast Ero1p is highly responsive to small changes in physiological levels of free FAD. This sensitivity underlies the dependence of oxidative protein folding on cellular FAD levels. FAD is synthesized in the cytosol but can readily enter the ER lumen and promote Ero1p-catalyzed oxidation. Ero1p then uses molecular oxygen as its preferred terminal electron acceptor. Thus Ero1p directly couples disulfide formation to the consumption of molecular oxygen, but its activity is modulated by free lumenal FAD levels, potentially linking disulfide formation to a cell's nutritional or metabolic status.

Original language	English (US)
Pages (from-to)	983-994
Number of pages	12
Journal	Molecular cell
Volume	10
Issue number	5
DOIs	https://doi.org/10.1016/S1097-2765(02)00696-2
State	Published - Nov 1 2002

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/S1097-2765(02)00696-2

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title = "The FAD- and O2-dependent reaction cycle of Ero1-mediated oxidative protein folding in the endoplasmic reticulum",

abstract = "The endoplasmic reticulum (ER) supports disulfide formation through an essential protein relay involving Ero1p and protein disulfide isomerase (PDI). We find that in addition to having a tightly associated flavin adenine dinucleotide (FAD) moiety, yeast Ero1p is highly responsive to small changes in physiological levels of free FAD. This sensitivity underlies the dependence of oxidative protein folding on cellular FAD levels. FAD is synthesized in the cytosol but can readily enter the ER lumen and promote Ero1p-catalyzed oxidation. Ero1p then uses molecular oxygen as its preferred terminal electron acceptor. Thus Ero1p directly couples disulfide formation to the consumption of molecular oxygen, but its activity is modulated by free lumenal FAD levels, potentially linking disulfide formation to a cell's nutritional or metabolic status.",

author = "Tu, {Benjamin P.} and Weissman, {Jonathan S.}",

note = "Funding Information: The authors wish to thank C. Turck for assistance with mass spectroscopy, D. Kellogg for the yeast genomic library, D. Ron for sharing results prior to publication, and V. Massey, W. Lim, E. O'Shea, and members of the Weissman lab for helpful discussions. This work was supported by HHMI, Packard Foundation, Searle Scholars, and the National Institutes of Health, and an HHMI Predoctoral Fellowship (B.P.T.).",

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doi = "10.1016/S1097-2765(02)00696-2",

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T1 - The FAD- and O2-dependent reaction cycle of Ero1-mediated oxidative protein folding in the endoplasmic reticulum

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AU - Weissman, Jonathan S.

N1 - Funding Information: The authors wish to thank C. Turck for assistance with mass spectroscopy, D. Kellogg for the yeast genomic library, D. Ron for sharing results prior to publication, and V. Massey, W. Lim, E. O'Shea, and members of the Weissman lab for helpful discussions. This work was supported by HHMI, Packard Foundation, Searle Scholars, and the National Institutes of Health, and an HHMI Predoctoral Fellowship (B.P.T.).

PY - 2002/11/1

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N2 - The endoplasmic reticulum (ER) supports disulfide formation through an essential protein relay involving Ero1p and protein disulfide isomerase (PDI). We find that in addition to having a tightly associated flavin adenine dinucleotide (FAD) moiety, yeast Ero1p is highly responsive to small changes in physiological levels of free FAD. This sensitivity underlies the dependence of oxidative protein folding on cellular FAD levels. FAD is synthesized in the cytosol but can readily enter the ER lumen and promote Ero1p-catalyzed oxidation. Ero1p then uses molecular oxygen as its preferred terminal electron acceptor. Thus Ero1p directly couples disulfide formation to the consumption of molecular oxygen, but its activity is modulated by free lumenal FAD levels, potentially linking disulfide formation to a cell's nutritional or metabolic status.

AB - The endoplasmic reticulum (ER) supports disulfide formation through an essential protein relay involving Ero1p and protein disulfide isomerase (PDI). We find that in addition to having a tightly associated flavin adenine dinucleotide (FAD) moiety, yeast Ero1p is highly responsive to small changes in physiological levels of free FAD. This sensitivity underlies the dependence of oxidative protein folding on cellular FAD levels. FAD is synthesized in the cytosol but can readily enter the ER lumen and promote Ero1p-catalyzed oxidation. Ero1p then uses molecular oxygen as its preferred terminal electron acceptor. Thus Ero1p directly couples disulfide formation to the consumption of molecular oxygen, but its activity is modulated by free lumenal FAD levels, potentially linking disulfide formation to a cell's nutritional or metabolic status.

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JO - Molecular cell

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The FAD- and O₂-dependent reaction cycle of Ero1-mediated oxidative protein folding in the endoplasmic reticulum

Abstract

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