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 oligosaccharides in eukaryotic cells, it has been appreciated for some time that they are integral components of the polymannose oligosaccharides of newly 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)GlcNAc(2)) from a dolichyl pyrophosphoryl carrier to asparagine in Asn-X-Ser(Thr) sequences on the polypeptide chain (2, 3). Moreover, it has recently become apparent that the most internal of the three glucose residues, after being brought to a terminal position through the action of ER1-situated glucosidases, interacts with lectin-like chaperones to mediate proper folding and/or oligomerization during protein quality control (4, 5). From these observations it has become evident that the presence of transient glucose residues on the polymannose oligosaccharides provides ideal recognition signals for crucial biological events, which have implications for a number of disease states as well as for viral replication. A rather complicated enzymatic machinery occurs in eukaryotic cells to achieve glucose attachment (6) and removal (7, 8), and this has been studied effectively with the help of mutants and inhibitors. It is the purpose of this article to provide a succinct overview of this distinctive area of glycobiology.