Figure 2.
General proteoglycan biosynthetic steps involved in GAG chain initiation, elongation and modifications
(A) Biosynthesis of the backbone structure of heparan sulfate. The protein core provides a Ser residue that forms a linkage with a Xyl-Gal-Gal-GlcA tetrasaccharide. For HS biosynthesis, a GlcNAc residue is added to the tetrasaccharide linkage via exostosin like glycosyltransferase 3 (EXTL3). Subsequently, EXTL1 and EXTL2 add alternating GlcA and GlcNAc to the chain.
(B) The progressive GAG chain modification leads to diverse structures of sulfated and unsulfated GAGS. The representative structures of heparan sulfate, chondroitin sulfate, dermatan sulfate, hyaluronan, and keratan sulfate (which are linked to an Asp residue instead of a Ser) are shown respectively. We note that we are not discussing the detailed biosynthesis and structure of hyaluronan since this subject has been covered extensively in recent literature.298,299,311 For additional information and details, please refer to the text. The schematic was adapted from Esko and Selleck8 and McMillan et al.15