The thiol-dependent reductase ERp57 interacts specifically with N-glycosylated integral membrane proteins.
The lumen of the endoplasmic reticulum contains a number of distinct molecular chaperones and folding factors, which modulate the folding and assembly of newly synthesized proteins and protein complexes. A subset of these luminal components are specific for glycoproteins, and, like calnexin and calreticulin, the thiol-dependent reductase ERp57 has been shown to interact specifically with soluble secretory proteins bearing N-linked carbohydrate. Calnexin and calreticulin also interact with glycosylated integral membrane proteins, and in this study we have examined the interaction of ERp57 with these substrates. As with soluble proteins, the binding of ERp57 to an integral membrane protein is dependent upon the protein bearing an N-glycan that has undergone glucose trimming. Furthermore, ERp57 binds to newly synthesized glycoproteins in combination with either calnexin or calreticulin. We propose that ERp57 acts in concert with calnexin and calreticulin to modulate glycoprotein folding and enforce the glycoprotein specific quality control mechanism operating in the endoplasmic reticulum.
Elliott
J G
JG
School of Biological Sciences, University of Manchester, 2.205 Stopford Building, Oxford Road, Manchester M13 9PT, United Kingdom.
Oliver
J D
JD
High
S
S
D000818:Animals; D001324:Autoantigens / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D037281:Calnexin; D037282:Calreticulin; D004285:Dogs; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1; D006021:Glycophorins / Q000378:metabolism*; D006031:Glycosylation; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007535:Isomerases; D037102:Lectins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008861:Microsomes / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D010179:Pancreas / Q000166:cytology; D010750:Phosphoproteins / Q000378:metabolism; D011485:Protein Binding; D019704:Protein Disulfide-Isomerases; D017510:Protein Folding; D051381:Rats; D012261:Ribonucleoproteins / Q000378:metabolism
D001324:Autoantigens; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D051272:Glucose Transporter Type 1; D006021:Glycophorins; D006360:Heat-Shock Proteins; D037102:Lectins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D009004:Monosaccharide Transport Proteins; D010750:Phosphoproteins; D012261:Ribonucleoproteins; D037281:Calnexin; D007535:Isomerases; C513196:PDIA3 protein, rat; D019704:Protein Disulfide-Isomerases; D005947:Glucose