Article

Ero1p Oxidizes Protein Disulfide Isomerase in a Pathway for Disulfide Bond Formation in the Endoplasmic Reticulum

Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
Molecular Cell (Impact Factor: 14.46). 11/1999; 4(4):469-77. DOI: 10.1016/S1097-2765(00)80198-7
Source: PubMed

ABSTRACT Native protein disulfide bond formation in the endoplasmic reticulum (ER) requires protein disulfide isomerase (PDI) and Ero1p. Here we show that oxidizing equivalents flow from Ero1p to substrate proteins via PDI. PDI is predominantly oxidized in wild-type cells but is reduced in an ero1-1 mutant. Direct dithiol-disulfide exchange between PDI and Ero1p is indicated by the capture of PDI-Ero1p mixed disulfides. Mixed disulfides can also be detected between PDI and the ER precursor of carboxypeptidase Y (CPY). Further, PDI1 is required for the net formation of disulfide bonds in newly synthesized CPY, indicating that PDI functions as an oxidase in vivo. Together, these results define a pathway for protein disulfide bond formation in the ER. The PDI homolog Mpd2p is also oxidized by Ero1p.

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    • "Here, the thiol group can undergo reversible oxidation into sulfenic acid or irreversible oxidation into sulfinic-or sulfonic acid; the thiol group can also be S-glutathionylated or, if reactive nitrogen species are present, nitrosylated. Proteins undergoing oxidative folding within the ER gain disulfides by dithiol-disulfide exchange with the oxidized form of the thioredoxin-like protein Pdi1p (Frand & Kaiser, 1999; Tu & Weissman, 2004). A shift to hyperoxidizing conditions within the ER, however, will inactivate Ero1p which acts as a catalyst for Pdi1p, and thus can lead to an increased presence of reduced thiols in protein domains (such as the EF-SAM domain of STIM) located in the ER lumen (Sevier et al. 2007). "
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