Overproduction of Mpd2p Suppresses the Lethality of Protein Disulfide Isomerase Depletion in a CXXC Sequence Dependent Manner

The third multicopy suppressor gene of thePDI1deletion fromSaccharomyces cerevisiae, MPD2,was isolated and characterized. TheMPD2gene encodes a protein with a putative signal sequence, ER retention signal, and a disulfide isomerase active site like sequence. The amino acid sequence around the active site like sequence is similar to the thioredoxin-like domains of PDI and PDI related proteins, although the similarity is comparatively low. A Δ-pdi1strain overproducing Mpd2p showed slow growth and was sensitive to 1 mM dithiothreitol. Mpd2p can be detected in wild type cells and is a glycoprotein. Although theMPD2gene was not essential for growth, overexpression of the gene partially restored the maturation defect of carboxypeptidase Y caused by thePDI1deletion. Mutagenesis analysis revealed that Mpd2p can compensate for the loss of PDI with its CXXC sequence.