O-glycosylation

O-linked glycosylation is the attachment of a sugar molecule to the oxygen atom of serine (Ser) or threonine (Thr) residues in a protein. O-glycosylation is a post-translational modification that occurs after the protein has been synthesised. In eukaryotes, it occurs in the endoplasmic reticulum, Golgi apparatus and occasionally in the cytoplasm; in prokaryotes, it occurs in the cytoplasm. Several different sugars can be added to the serine or threonine, and they affect the protein in different ways by changing protein stability and regulating protein activity. O-glycans, which are the sugars added to the serine or threonine, have numerous functions throughout the body, including trafficking of cells in the immune system, allowing recognition of foreign material, controlling cell metabolism and providing cartilage and tendon flexibility. Because of the many functions they have, changes in O-glycosylation are important in many diseases including cancer, diabetes and Alzheimer's. O-glycosylation occurs in all domains of life, including eukaryotes, archaea and a number of pathogenic bacteria including Burkholderia cenocepacia, Neisseria gonorrhoeae and Acinetobacter baumannii. Addition of N-acetylgalactosamine (GalNAc) to a serine or threonine occurs in the Golgi apparatus, after the protein has been folded. The process is performed by enzymes known as GalNAc transferases (GALNTs), of which there are 20 different types. The initial O-GalNAc structure can be modified by the addition of other sugars, or other compounds such as methyl and acetyl groups. These modifications produce 8 core structures known to date. Different cells have different enzymes that can add further sugars, known as glycosyltransferases, and structures therefore change from cell to cell. Common sugars added include galactose, N-acetylglucosamine, fucose and sialic acid. These sugars can also be modified by the addition of sulfates or acetyl groups. GalNAc is added onto a serine or threonine residue from a precursor molecule, through the activity of a GalNAc transferase enzyme.