Biochemical basis of oxidative protein folding in the endoplasmic reticulum

B. P. Tu, S. C. Ho-Schleyer, K. J. Travers, J. S. Weissman

Research output: Contribution to journalArticle

320 Citations (Scopus)

Abstract

The endoplasmic reticulum (ER) supports disulfide bond formation by a poorly understood mechanism requiring protein disulfide isomerase (PDI) and ERO1. In yeast, Ero1p-mediated oxidative folding was shown to depend on cellular flavin adenine dinucleotide (FAD) levels but not on ubiquinone or heme, and Ero1p was shown to be a FAD-binding protein. We reconstituted efficient oxidative folding in vitro using FAD, PDI, and Ero1p. Disulfide formation proceeded by direct delivery of oxidizing equivalents from Ero1p to folding substrates via PDI. This kinetic shuttling of oxidizing equivalents could allow the ER to support rapid disulfide formation while maintaining the ability to reduce and rearrange incorrect disulfide bonds.

Original languageEnglish (US)
Pages (from-to)1571-1574
Number of pages4
JournalScience
Volume290
Issue number5496
StatePublished - Nov 24 2000

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Protein Folding
Protein Disulfide-Isomerases
Endoplasmic Reticulum
Disulfides
Flavin-Adenine Dinucleotide
Ubiquinone
Heme
Carrier Proteins
Yeasts

ASJC Scopus subject areas

  • General

Cite this

Tu, B. P., Ho-Schleyer, S. C., Travers, K. J., & Weissman, J. S. (2000). Biochemical basis of oxidative protein folding in the endoplasmic reticulum. Science, 290(5496), 1571-1574.

Biochemical basis of oxidative protein folding in the endoplasmic reticulum. / Tu, B. P.; Ho-Schleyer, S. C.; Travers, K. J.; Weissman, J. S.

In: Science, Vol. 290, No. 5496, 24.11.2000, p. 1571-1574.

Research output: Contribution to journalArticle

Tu, BP, Ho-Schleyer, SC, Travers, KJ & Weissman, JS 2000, 'Biochemical basis of oxidative protein folding in the endoplasmic reticulum', Science, vol. 290, no. 5496, pp. 1571-1574.
Tu BP, Ho-Schleyer SC, Travers KJ, Weissman JS. Biochemical basis of oxidative protein folding in the endoplasmic reticulum. Science. 2000 Nov 24;290(5496):1571-1574.
Tu, B. P. ; Ho-Schleyer, S. C. ; Travers, K. J. ; Weissman, J. S. / Biochemical basis of oxidative protein folding in the endoplasmic reticulum. In: Science. 2000 ; Vol. 290, No. 5496. pp. 1571-1574.
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