Glucose residues as key determinants in the biosynthesis and quality control of glycoproteins with N-linked oligosaccharides

Although glucose residues do not occur as constituents of mature N-linked o ligosaccharides in eukaryotic cells, it has been appreciated for some time that they are integral components of the polymannose oligosaccharides of ne wly synthesized glycoproteins and their lipid-linked precursors (1). Indeed it has been shown that they play an essential role in the cotranslational. transfer of a preassembled triglucosylated oligosaccharide (Glc(3)Man(9)Gl cNAc(2)) from a dolichyl pyrophosphoryl carrier to asparagine in Asn-X-Ser( Thr) sequences on the polypeptide chain (2, 3). Moreover, it has recently b ecome apparent that the most internal of the three glucose residues, after being brought to a terminal position through the action of ER1-situated glu cosidases, interacts with lectin-like chaperones to mediate proper folding and/or oligomerization during protein quality control (4, 5). From these ob servations it has become evident that the presence of transient glucose res idues on the polymannose oligosaccharides provides ideal recognition signal s for crucial biological events, which have implications for a number of di sease states as well as for viral replication. A rather complicated enzymat ic machinery occurs in eukaryotic cells to achieve glucose attachment (6) a nd removal (7, 8), and this has been studied effectively with the help of m utants and inhibitors. It is the purpose of this article to provide a succi nct overview of this distinctive area of glycobiology.