title: Novel covalent chaperone complexes associated with human chorionic gonadotropin beta subunit folding intermediates.
abstract: Molecular chaperones facilitate the folding of proteins in the endoplasmic reticulum (ER) of mammalian cells. The glycoprotein hormone chorionic gonadotropin beta subunit is a secretory protein whose folding in the ER has been demonstrated (Huth, J. R., Mountjoy, K., Perini, F., and Ruddon, R. W.(1992) J. Biol. Chem. 267, 8870-8879). Because folding of wild type hCG-beta subunit occurs in the ER with a t1/2 = 4-5 min, stable association of ER chaperones with hCG-beta have been difficult to detect probably because they have a short half-life. However, beta-chaperone complexes containing the ER chaperones BiP, ERp72, and ERp94 have been detected in slow folding mutants of hCG-beta subunit that lack both of the N-linked oligosaccharides (Feng, W., Matzuk, M. M., Mountjoy, K., Bedows, E., Ruddon, R. W., and Boime, I. (1995) J. Biol. Chem. 270, 11851-11859). The questions addressed here are 1) whether the detection of chaperone-containing complexes is related to the absence of carbohydrate or to the rate of hCG-beta subunit folding, 2) whether such complexes are dead-end or whether they lead to formation of a secreted, mature hCG-beta form, and 3) what the nature of the hCG-beta-chaperone binding is. The data obtained indicate that the amount of detectable hCG-beta-chaperone complexes correlates with the rate or extent of folding, that the complexes of hCG-beta with ER chaperones lead to the formation of secretable beta, and that the complexes of hCG-beta with chaperones involve the formation of intermolecular disulfide bonds.
authors.affiliation: The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA.
authors.forename: W
authors.initials: W
authors.lastname: Feng
authors.forename: E
authors.initials: E
authors.lastname: Bedows
authors.forename: S E
authors.initials: SE
authors.lastname: Norton
authors.forename: R W
authors.initials: RW
authors.lastname: Ruddon
mesh_terms: D000818:Animals; D016466:CHO Cells; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006224:Cricetinae; D004220:Disulfides / Q000737:chemistry; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006031:Glycosylation; D006207:Half-Life; D006801:Humans; D066298:In Vitro Techniques; D018832:Molecular Chaperones / Q000737:chemistry* / Q000378:metabolism; D015394:Molecular Structure; D009154:Mutation; D017510:Protein Folding; D014162:Transfection
chemical_list: D018997:Chorionic Gonadotropin, beta Subunit, Human; D004220:Disulfides; D018832:Molecular Chaperones