Most cell surface and secreted proteins are modified by the addition of
N-glycosyl and
O-glycosyl oligosaccharides, the functions of which, in many cases, remain unclear. The roles of protein glycosylation were first studied using enzyme inhibitors, glycosidases and cell mutants with altered sugar addition or modification enzymes. More recently, site-directed mutagenesis has allowed the targeting of specific oligosaccharides on a single protein species. Loss of
N-linked oligosaccharides from glycoproteins often results in altered disulfide bonding and leads to the formation of aggregates probably resulting from an anomalous protein conformation. The misfolded proteins are frequently retained in the endoplasmic reticulum where they may be degraded. Many receptors lacking
N-linked oligosaccharides fail to bind their ligands, again suggesting that they may be misfolded. Site-directed mutagenesis has demonstrated that individual sugar chains may have different functions in a glycoprotein and one sugar chain may have a dominant effect on the acquisition of the correct conformation. In some cases, once the correct conformation has been achieved,
N-glycosyl chains appear to be dispensable. The role of
O-glycosyl chains in glycoprotein function is less well understood and, where they have been studied, their loss seems to have little effect in proteins produced by many cultured cells. It is likely that these sugar chains play a role that is only apparent in multicellular situations.
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