Oglykosylation

Oglykosylation refers to the addition of sugar moieties to the oxygen atom of hydroxyl-containing amino acids in proteins, most commonly serine and threonine. It is a form of protein glycosylation that occurs in different cellular contexts and serves diverse functions. The best-known form is mucin-type O-glycosylation, which begins in the Golgi apparatus with the transfer of N-acetylgalactosamine (GalNAc) to Ser or Thr by polypeptide N-acetylgalactosaminyltransferases (ppGalNAcTs). This GalNAc residue can be elaborated into core structures, such as core 1 (Galβ1-3GalNAc) and core 2, and then extended with other sugars like galactose, N-acetylneuraminic acid (sialic acid), and fucose. Mucin-type O-glycosylation is prevalent on secreted and cell-surface glycoproteins, especially mucins, and influences protein stability, protease resistance, receptor interactions, and immune recognition.

A second, distinct form is O-linked GlcNAc (O-GlcNAc), an intracellular modification found primarily in the nucleus and cytoplasm. O-GlcNAc is added to Ser or Thr by O-GlcNAc transferase (OGT) and removed by O-GlcNAcase (OGA). Unlike mucin-type O-glycans, O-GlcNAc generally exists as a single monosaccharide and participates in dynamic regulation, often in concert with phosphorylation to modulate signaling, transcription, and metabolism.

Collagen and some proteoglycans also bear O-linked glycans on hydroxylysine residues, typically with galactose or glucose–galactose disaccharides, contributing to structural integrity.

Clinical relevance: dysregulation of O-glycosylation is linked to cancer, inflammatory diseases, and congenital disorders of glycosylation. Analytical approaches include mass spectrometry and glycan sequencing.