PROTEIN-FOLDING IN THE ENDOPLASMIC-RETICULUM - LESSONS FROM THE HUMANCHORIONIC-GONADOTROPIN BETA-SUBUNIT

There have been few studies of protein folding in the endoplasmic reti culum of intact mammalian cells. In the one case where the in vivo and in vitro folding pathways of a mammalian secretory protein have been compared, the folding of the human chorionic gonadotropin beta subunit (hCG-beta), the order of formation of the detected folding intermedia tes is the same. The rate and efficiency with which multidomain protei ns such as hCG-beta fold to native structure in intact cells is higher than in vitro, although intracellular rates of folding of the beta su bunit can be approached in vitro in the presence of an optimal redox p otential and protein disulfide isomerase. Understanding how proteins f old in vivo may provide a new way to diagnose and treat human illnesse s that occur due to folding defects.