Glycoproteins - Hughes R. 1985

Biosynthesis
Assembly of N-glycans
Processing

When studying the oligosaccharide Structure of a large lipid intermediate (Fig. 3.5), it was found to share many features with already known N-glycans in Glycoproteins. The core region consists of a ß-mannosyl residue linked to a chitobiose unit, which is typically found in N-glycans. Furthermore, the environment of the a-mannosyl residues attached to this core is identical to that of the lipid intermediate, such as in the large oligomannose unit of IgM (Fig. 2.8). However, several structural differences between the precursor and glycoprotein glycans should be noted. First, lipid-linked Oligosaccharides contain three glucose residues, whereas glucose is generally never found in asparagine-linked oligosaccharides. Second, it is necessary to explain how many other oligomannose structures arise in glycoproteins, such as those in Ovalbumin (Fig. 2.6). Finally, how are such complex N-glycans that make up Orosomucoid assembled? Currently, it appears quite likely that all these structures are formed As a result of transfer from a common glucose-containing dolichol derivative. Following transfer to the polypeptide chain, the complex lipid-linked oligosaccharides undergo extensive modification. Such modifications are carried out through a complex series of reactions known as processing. Often, upon attachment to the polypeptide, the glucose residue is removed by a highly specific a-glucosidase [32]. The a-mannose residues are removed by a set of specific a-mannosidases [33], presumably in a specific sequence [34] which, at least in some cases, differs from that of their assembly in the lipid intermediate (Fig. 3.6). During processing (Fig. 3.6), many oligomannose glycans are found as stable components of mature, fully formed glycoproteins, such as region (b) of immunoglobulin M (Fig. 2.8). It is likely that controlled processing accounts for The Emergence of the set of oligomannose glycoprotein structures, although it cannot be ruled out that more complex biosynthetic pathways are involved; for instance, complete processing leading to structures with five mannose residues is accompanied by the resynthesis of glycans with a higher mannose content. It is also possible that alternative processing pathways account for the presence of various oligomannose structures in region (a) of immunoglobulin M (Fig. 2.8). To date, nothing is known about the factors controlling processing and how the required Cleavage of mannose residues is directed in accordance with a specific glycosylation site on the same polypeptide. Such variations, depending on The Cell type or animal species, could lead to The formation of discrete glycan chains characteristic of those Cells and contribute to the structural diversity of N-glycans.