Figure 3.

Schematic Representation of the PG Biosynthesis

XT-I and XT-II participate in the initiation of the PG biosynthesis by transferring a Xyl to specific Ser residues of the core protein. Two Gal and one GlcUA will be sequentially added via the action of GalT-I, GalT-II, and GlcAT-I to form the common linker region. The addition of a GalNAc will then initiate the assembly of chondroitin-sulfate/dermatan-sulfate (CS/DS) chains while addition of a GlcNAc will initiate the synthesis toward heparan-sulfate/heparin (HS/Hep) chains. Mutations in genes involved in the assembly of the common linker region have been associated with several disorders, namely DBQD type 2 (XYLT1), Ehlers-Danlos progeroid syndrome, type 1 (B4GALT7), Ehlers-Danlos progeroid syndrome, type 2/spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMD-JL1) (B3GALT6), and Larsen-like syndrome (B3GAT3).