Sequence of protein disulphide isomerase and implications of its relationship to thioredoxin.
The formation of disulphide bonds is essential to the structure and function of proteins. These bonds rapidly form either cotranslationally or immediately post-translationally in the lumen of the endoplasmic reticulum. Native disulphide pairing for such proteins has been achieved in vitro; however, the rates of reassembly are slow and the conditions non-physiological. To account for these observations, Anfinsen et al. proposed that a 'disulphide interchange protein' was the in vivo catalyst of disulphide bond rearrangement. Other groups discovered an activity with similar characteristics that catalysed the reductive cleavage of insulin and may be associated with insulin degradation, although this result has been disputed. The enzyme involved, protein disulphide isomerase (PDI; EC 5.3.4.1), may be the in vivo catalyst of disulphide bond formation. Here we describe the sequence of cloned rat liver PDI complementary DNA which predicts a protein with two distinct regions homologous with Escherichia coli thioredoxin, a known cofactor in oxidation-reduction reactions. Each of these regions contains the presumed active site sequence Trp-Cys-Gly-His-Cys-Lys, suggesting that PDI, similar in action to thioredoxin, catalyses disulphide bond interchange via an internal disulphide-sulphydryl interchange. The cDNA predicts a signal peptide consistent with the view that PDI is a luminal endoplasmic reticulum protein. PDI messenger RNA, although ubiquitous, is more highly concentrated in secretory cells.
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D004247:DNA / Q000032:analysis; D007535:Isomerases / Q000235:genetics*; D010179:Pancreas / Q000201:enzymology; D014176:Protein Biosynthesis; D019704:Protein Disulfide-Isomerases; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D051381:Rats; D012156:Reticulocytes / Q000378:metabolism; D013329:Structure-Activity Relationship; D013879:Thioredoxins / Q000235:genetics*
D001426:Bacterial Proteins; D012333:RNA, Messenger; D013879:Thioredoxins; D004247:DNA; D007535:Isomerases; D019704:Protein Disulfide-Isomerases