The yeast EUG1 gene encodes an endoplasmic reticulum protein that is functionally related to protein disulfide isomerase.

Abstract

The product of the EUGI gene of Saccharomyces cerevisiae is a soluble endoplasmic reticulum protein with homology to both the mammalian protein disulfide isomerase (PDI) Protein translocation across membranes requires that proteins assume an unfolded conformation (8, 13). Proteins entering the secretory pathway are translocated across the endoplasmic reticulum (ER) membrane, and these newly synthesized proteins assume their native conformation prior to export from the ER (9, 22). Interactions between the nascent, folding polypeptides and resident ER proteins may aid in newly synthesized proteins achieving a native conformation (23). Proposed interactions include binding to BiP to prevent aggregation and to promote folding and oligomerization (22, 41) and isomerization by protein disulfide isomerase (PDI) to assist in the formation of native disulfide bonds (20, 24).Many secretory proteins undergo disulfide bond formation in the oxidizing environment of the ER lumen. Several lines of evidence suggest that PDI participates in the folding of proteins containing disulfide bonds. PDI was originally characterized for its ability to catalyze the steps in the in vitro refolding of RNase A (24), bovine pancreatic trypsin inhibitor (10), and collagen (35), all of which require disulfide bond rearrangements. More recently, it was demonstrated that ER microsomes depleted of PDI by a high-pH wash were able to translocate and glycosylate -y-

The protein disulphide-isomerase family: unravelling a string of folds

“…In light of the preceding discussion on the role of the Nterminal Cys residue within the thioredoxin box in isomerase activity, it is not surprising to learn that Eug1p, a PDI-related protein with active-site sequences -Cys-Leu-His-Ser-and CysIle-His-Ser- [80], can complement the isomerase deficiency of PDI-deficient yeast, and yet cannot effect maturation of carboxypeptidase Y [79] to wild-type levels. Integrity of the reactive site of the first a domain of PDI is clearly more important for maturation of carboxypeptidase Y than is the ah domain.…”

Hut1 proteins identified in Saccharomyces cerevisiae and Schizosaccharomyces pombe are functional homologues involved in the protein‐folding process at the endoplasmic reticulum

“…Although the essential function of Pdi1p in yeast cells is considered to be the isomerization of non-native disulphide bonds (Laboissiere et al, 1995), several lines of evidence indicate that Pdi1p also catalyses the oxidation of secretory proteins (Lyles and Gilbert, 1991;Frand and Kaiser, 1999). S. cerevisiae carries four additional PDI-related proteins (Mpd1p, Mpd2p, Eug1p and Eps1p) (Tachikawa et al, 1995(Tachikawa et al, , 1997Tachibana and Stevens, 1992;Wang and Chang, 1999). Mpd1p, Mpd2p and Eps1p have a single active-site motif of CXXC, and Eug1p has two active-site motifs of CXXS.…”

Sulfhydryl Oxidation, Not Disulfide Isomerization, Is the Principal Function of Protein Disulfide Isomerase in Yeast Saccharomyces cerevisiae

“…In the yeast Saccharomyces cerevisiae, deletion of the PDI1 gene is lethal (2). A mutant PDI in which all the active site cysteines have been replaced with serines (N SGHS -C SGHS ) is still an active chaperone and has other, secondary activities of PDI in vitro, but it is incapable of complementing the PDI1 deletion.…”

“…Protein disulfide isomerase (PDI) 1 is an essential ER folding assistant present in all eukaryotes that facilitates the folding of disulfide-containing proteins (2). PDI catalysis of oxidative protein folding consists of two types of reactions, oxidation of free sulfhydryls into disulfides (oxidase activity) and rearrangement of incorrectly formed disulfides (isomerase activity) (1).…”