Wj. Feng et al., NOVEL COVALENT CHAPERONE COMPLEXES ASSOCIATED WITH HUMAN CHORIONIC-GONADOTROPIN BETA-SUBUNIT FOLDING INTERMEDIATES, The Journal of biological chemistry, 271(31), 1996, pp. 18543-18548
Molecular chaperones facilitate the folding of proteins in the endopla
smic reticulum (ER) of mammalian cells, The glycoprotein hormone chori
onic 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 foldi
ng of wild type hCG-beta subunit occurs in the ER with a t(1/2) = 4-5
min, stable association of ER chaperones with hCG-beta have been diffi
cult 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 t
hat lack both of the N-linked oligosaccharides (Feng, W,, Matzuk, M, M
,, Mountjoy, K., Bedows, E,, Ruddon, R, W,, and Boime, I, (1995) J, Bi
ol, Chem, 270, 11851-11859), The questions addressed here are 1) wheth
er the detection of chaperone-containing complexes is related to the a
bsence 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 o
r extent of folding, that the complexes of hCG-beta with ER chaperones
lead to the formation of secretable beta, and that the complexes of h
CG-beta with chaperones involve the formation of intermolecular disulf
ide bonds.