Fig. 7: Molecular mechanism of CS chain polymerization.

Illustration of the proposed mechanism for chain elongation by the CS polymerase complex CHSY3-CHPF. In a first reaction step, a GlcA residue is added onto the proteoglycan carrying a pentasaccharide-linker by the N-terminal GT domain of CHSY3. The generated hexasaccharide product is released and binds to the C-terminal GT domain of CHSY3, exhibiting GalNAc transferase activity. Upon GalNAc addition, the proteoglycan dissociates, and a new reaction cycle starts. Repetitive addition of GlcA and GalNAc residues leads to the generation of the long chondroitin sulfate backbone.