Differential cooperative enzymatic activities of protein disulfide isomerase family in protein folding.
Endoplasmic reticulum (ER)p61, ERp72, and protein disulfide isomerase (PDI), which are members of the PDI family protein, are ubiquitously present in mammalian cells and are thought to participate in disulfide bond formation and isomerization. However, why the 3 different members need to be colocalized in the ER remains an enigma. We hypothesized that each PDI family protein might have different modes of enzymatic activity in disulfide bond formation and isomerization. We purified PDI, ERp61, and ERp72 proteins from rat liver microsomes and compared the effects of each protein on the folding of bovine pancreatic trypsin inhibitor (BPTI). ERp61 and ERp72 accelerated the initial steps more efficiently than did PDI. ERp61 and ERp72, however, accelerated the rate-limiting step less efficiently than did PDI. PDI or ERp72 did not impede the folding of BPTI by each other but rather catalyzed the folding reaction cooperatively with each other. These data suggest that differential enzymatic activities of ERp proteins and PDI represent a complementary contribution of these enzymes to protein folding in the ER.
Satoh
Mamoru
M
Department of Pathology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi 480-0392, Japan.
Shimada
Atsuyoshi
A
Kashiwai
Akiko
A
Saga
Shinsuke
S
Hosokawa
Masanori
M
D000818:Animals; D007611:Aprotinin; D002384:Catalysis; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000201:enzymology* / Q000378:metabolism; D004791:Enzyme Inhibitors; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007535:Isomerases / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008862:Microsomes, Liver / Q000201:enzymology* / Q000378:metabolism; D019704:Protein Disulfide-Isomerases / Q000737:chemistry / Q000378:metabolism*; D017510:Protein Folding; D051381:Rats; D013997:Time Factors
D004220:Disulfides; D004791:Enzyme Inhibitors; D006360:Heat-Shock Proteins; D008562:Membrane Glycoproteins; C062477:endoplasmic reticulum glycoprotein p72; D007611:Aprotinin; D007535:Isomerases; C513196:PDIA3 protein, rat; D019704:Protein Disulfide-Isomerases