Heavy-chain binding protein recognizes aberrant polypeptides translocated in vitro.
Immunoglobulin heavy-chain binding protein (BiP, GRP-78) associates tightly in the endoplasmic reticulum (ER) with newly synthesized proteins that are incompletely assembled, have mutant structures, or are incorrectly glycosylated. The function of BiP has been suggested to be to prevent secretion of incorrectly folded or incompletely assembled protein, to promote folding or assembly of proteins, or to solubilize protein aggregates within the ER lumen. Here we examine the interaction of BiP with newly synthesized polypeptides in an in vitro protein translation-translocation system. We find that BiP forms tight complexes with nonglycosylated yeast invertase and incorrectly disulphide-bonded prolactin, but does not associate detectably with either glycosylated invertase or correctly disulphide-bonded prolactin. Moreover, BiP associates detectably only with completed chains of prolactin, not with chains undergoing synthesis. We conclude that BiP recognizes and binds with high affinity in vitro to aberrantly folded or aberrantly glycosylated polypeptides, but not to all nascent chains as they are folding.
D002352:Carrier Proteins / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006026:Glycoside Hydrolases / Q000235:genetics; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism*; D018832:Molecular Chaperones; D008970:Molecular Weight; D014176:Protein Biosynthesis; D011498:Protein Precursors / Q000235:genetics; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic; D043324:beta-Fructofuranosidase
D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D007143:Immunoglobulin Heavy Chains; D018832:Molecular Chaperones; D011498:Protein Precursors; D011506:Proteins; D012333:RNA, Messenger; D006026:Glycoside Hydrolases; D043324:beta-Fructofuranosidase