Biogenesis of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, an integral glycoprotein of the endoplasmic reticulum.

Using a cell line, C100, that overproduces 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase; EC 1.1.1.34) 100-fold, we have studied the synthesis and insertion of this protein into the endoplasmic reticulum. The enzyme is synthesized on membrane-bound polysomes. It is cotranslationally but not post-translationally inserted into dog pancreatic microsomes. This cotranslational insertion is dependent upon signal recognition particle. HMG-CoA reductase is glycosylated with an oligosaccharide(s) of the "high-mannose" type sensitive to endo-beta-D-N-acetylglucosaminidase H. Partial determination of the NH2-terminal amino acid sequence of the in vitro translation product and the mature polypeptide indicate they are the same and demonstrate there is no cleavage of an NH2-terminal signal sequence.