Folding of VSV G protein: sequential interaction with BiP and calnexin.
The endoplasmic reticulum (ER) contains molecular chaperones that facilitate the folding of proteins in mammalian cells. Biosynthetic labeling was used to study the interactions of two chaperones, BiP and calnexin, with vesicular stomatitis virus (VSV) glycoprotein (G protein). Coimmunoprecipitation of G protein with the chaperones showed that BiP bound maximally to early folding intermediates of G protein, whereas calnexin bound after a short lag to more folded molecules. Castanospermine, an inhibitor of ER glucosidases, blocked the binding of proteins to calnexin and inhibited G protein folding. Interaction with calnexin was necessary for efficient folding of G protein and for retention of partially folded forms.
Hammond
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Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510.
Helenius
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A
D000818:Animals; D016466:CHO Cells; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D037281:Calnexin; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism; D007212:Indolizines / Q000494:pharmacology; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D017510:Protein Folding; D014721:Vesicular stomatitis Indiana virus / Q000737:chemistry* / Q000502:physiology; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism; D054836:Indolizidines
D002135:Calcium-Binding Proteins; D037281:Calnexin; D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006023:Glycoproteins; D006360:Heat-Shock Proteins; D007212:Indolizines; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D014759:Viral Envelope Proteins; C028391:G protein, vesicular stomatitis virus; C037806:castanospermine; D054836:Indolizidines