InterPro domain: IPR037192

Ero1 and PDI form the disulfide relay system of the ER that supports correct disulfide bond formation of secretory proteins. This entry represents Ero1 (endoplasmic oxidoreductin-1) from yeasts and its homologues from mammals, Ero1-alpha and Ero1-beta. Ero1 is an flavoprotein that directly transfers disulfide bonds to disulfide isomerase PDI [ 1 , 2 , 3 ]. Ero1 acts as an thiol oxidoreductase responsible for catalyzing disulfide bond formation in nascent polypeptide substrates via electron transfer through protein disulfide isomerase (PDI) with oxygen acting as the final electron acceptor [ 4 ]. Newly generated disulfides are transferred from a FAD (flavin adenine dinucleotide)-associated active site via a "shuttle disulfide" cysteine pair in Ero1 to PDI and from there on to substrate proteins [ 5 , 6 , 7 ]. The activity of Ero1 is regulated by PDI (also known as Pdi1). This regulation of Ero1 through reduction and oxidation of regulatory bonds within Ero1 is essential for maintaining the proper redox balance in the ER [ 8 , 8 ].

ERO1 has a multihelical structure consisting of two four-helical bundles.

1. Pathways for protein disulphide bond formation. Trends Cell Biol. 10, 203-10
2. Two pairs of conserved cysteines are required for the oxidative activity of Ero1p in protein disulfide bond formation in the endoplasmic reticulum. Mol. Biol. Cell 11, 2833-43
3. Balanced Ero1 activation and inactivation establishes ER redox homeostasis. J. Cell Biol. 196, 713-25
4. Role of the ERO1-PDI interaction in oxidative protein folding and disease. Pharmacol Ther 210, 107525
5. Structure, mechanism, and evolution of Ero1 family enzymes. Antioxid Redox Signal 16, 790-9
6. The physiological functions of mammalian endoplasmic oxidoreductin 1: on disulfides and more. Antioxid Redox Signal 16, 1109-18
7. A PDI-catalyzed thiol-disulfide switch regulates the production of hydrogen peroxide by human Ero1. Free Radic Biol Med 83, 361-72
8. Low reduction potential of Ero1alpha regulatory disulphides ensures tight control of substrate oxidation. EMBO J. 27, 2988-97