Protein Glycosylation

Glycosylation, the most common post-translational modification for proteins, serves diverse functions. Adding sugars to proteins makes the proteins more resistant to proteolytic digestion. Glycosylated proteins can act as markers and receptors to promote cell-cell adhesion. Additionally, they have many essential quality control functions in the cell, such as correct protein folding and facilitating transport of misfolded proteins to the cytosol, which can be degraded.

Glycosylation occurs in successive stages of protein synthesis when the peptide moves from one Golgi cisterna to the next. For example, mannose is removed, and N-acetylglucosamine is added in the cis and medial cisternae. Similarly, galactose and sialic acid are added in the trans-Golgi cisterna.

Based on the amino acid sidechain to which glycans attach, glycosylated proteins or glycoproteins can have N-glycosidic and O-glycosidic bonds. N-linked oligosaccharides are carbohydrate units attached to the amide nitrogen of asparagine, whereas O-linked oligosaccharides are connected to the hydroxyl groups of serine and threonine residues. Glycosylation serves many purposes in protein folding, such as making the intermediates more soluble to prevent aggregation. Glycans can also act as biochemical markers of certain diseases. Recent interest in the study of such glycan markers has led scientists to investigate the “glyco-code.”  The glyco-code, analogous to the cell’s genome or the proteome, is information encoded by the structurally diverse carbohydrate forms and their conjugates. The complex glycan structures and their spatial distribution in different cells encode biological information presenting polysaccharides as the third alphabet of life.