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. 2020 Mar 31;10(11):4903–4928. doi: 10.7150/thno.42480

Figure 2.

Figure 2

Protein-associated glycan biosynthetic pathways. N-glycan biosynthesis begins at the endoplasmic reticulum (ER) membrane with the Glc3Man9GlcNAc2-P-P-Dol precursor transfer to Asn in Asn-X-Ser/Thr sequons of proteins by oligosaccharyltransferase (OST). Of note, “X” represents any amino acid except Pro. Subsequent N-glycan processing reactions take place in the ER from where glycoproteins exit to the Golgi apparatus carrying N-glycans with either eight or nine Man residues, termed oligomannose N-glycans. Further, biosynthesis of hybrid and complex N-glycans occurs in the medial-Golgi. Subsequent sugar additions diversify the repertoire of hybrid and complex N-glycans by elongation of branching GlcNAc residues, capping of elongated branches and N-glycan core sugar addition. Common terminal structures include sialyl lewis antigens, such as sialyl lewis A (SLeA) through the concerted action of beta-galactoside-alpha-2,3-sialyltransferase-III and IV (ST3Gal III and IV) as well as alpha-4-fucosyltransferases (α4-FucT). Mucin type O-glycan biosynthesis is initiated in the late ER or in Golgi compartments by the Polypeptide GalNAcT- mediated transfer of N-acetylgalactosamine (GalNAc) to Ser or Thr residues of proteins in a tissue- and cell-type-specific manner. This first biosynthetic steps yield the Tn antigen (GalNAcα1-Ser/Thr), the simplest form of mucin-type O-glycosylation. Tn antigen can be sialylated into the sialyl Tn (STn) antigen by N-acetylgalactosaminide alpha-2,6-sialyltransferase I (ST6GalNAc I), abrogating further chain extension, or it can be extended into the core 1 antigen (T antigen) by N-acetylgalactosamine 3-beta-galactosyltransferase 1 (C1Gal-T1). In turn, the core 1 structure can be capped with sialic acid residues through the action of N-acetylgalactosaminide alpha-2,6-sialyltransferase 2 (ST6GalNAc II) or ST3Gal I, giving rise to sialyl T and disialyl T antigens, again preventing further extension. On the other hand, T antigen can be extended into the core 2 glycan by core 2 beta-1,6-N-acetylglucosaminyltransferase-I or III (C2GnT-I, III). Extended O-glycan structures beyond the core 2 antigen can also display terminal structures similar to N-glycan such as SLeA.