PURIFICATION OF A 58-KDA PROTEIN (ER58) FROM MONKEY LIVER-MICROSOMES AND COMPARISON WITH PROTEIN-DISULFIDE ISOMERASE

A 58-kDa protein (ER58) was purified from monkey liver to apparent hom ogeneity. It accounts for more than 3% of microsomal proteins and is h ighly conserved among several mammalian species. The amino acid compos itions of the N-terminal part and that of two internal peptide fragmen ts present strong similarities with the sequence ascribed to phospholi pase C-alpha. Numerous proteins exhibiting a high similarity with this sequence have been isolated by other investigators. Their biological function is controversial. Our purified protein is not active as a pho sphatidylinositol-specific phospholipase C, protease or carnitine acyl transferase. Although less efficient than authentic protein-disulfide isomerase, ER58 catalyses the glutathione-dependent reduction of insu lin and the reorganization of disulfide bends of randomly oxidized (sc rambled) ribonuclease in reducing conditions. In contrast, ER58 is dev oid of oxidizing activity on thiol groups of reduced proteins. Many st udies suggest that the proteins bearing the phospholipase C-alpha sequ ence could be considered as protein-disulfide isomerase isozymes. Our results indicate that ER58 is not totally similar to protein-disulfide isomerase in performing thiol :protein-disulfide oxidoreductase react ions and suggest that the two proteins may exert distinct cellular fun ctions.