Abstract
N-Linked glycosylation is one of the most common protein modifications and can have profound effects on protein expression and function. These effects often depend on the number and position of N-linked oligosaccharides added to a protein during core-glycosylation. While the sequon, Asn-X-Ser/Thr, serves as a recognition signal for core-glycosylation, other protein signals must also control this process, since many Asn-X-Ser/Thr sequons are glycosylated inefficiently or are not glycosylated at all. A variety of experimental approaches have been used to define the signals which control core-glycosylation at specific Asn residues. These include comparisons of protein sequences near glycosylated and non-glycosylated sequons, use of sequon-containing peptides as oligosaccharide acceptors or inhibitors, and analysis of the glycosylation of sequons in recombinant proteins. Such studies reveal that a complex set of factors determines the efficiency of oligosaccharide addition at each Asn-X-Ser/Thr sequon. Amino acids near the Asn residue in a sequon can profoundly affect its oligosaccharide acceptor activity. A variety of other factors further modulate core-glycosylation efficiency by influencing the accessibility of sequons for glycosylation at a critical time during protein synthesis. Studies addressing these issues are reviewed.
