Keratan sulfate

Although keratan sulfates belong to the GAG family, their core structures and disaccharide repeats are also found on N- and O-GalNAc glycans. Indeed, the repeats of Gal(b1-4)GlcNAc(b1-3) are also known as poly-N-acetyllactosamines. Most keratan sulfate chains occur on N-glycans, which are defined as keratan sulfate type I. Keratan sulfate chains on O-GalNAc glycans, called type II, are mainly found on the large proteoglycan aggrecan. Because aggrecan is a major constituent of cartilage, keratan sulfate type II is sometimes called skeletal keratan sulfate.

Keratan sulfate chains are extensively sulfated at the 6-O position of Gal and GlcNAc. Sulfation takes place during the chain polymerization process, with GlcNAc 6-O sulfotransferase acting only on non-reducing terminal GlcNAc. By contrast, Gal 6-O sulfation occurs on terminal or internal Gal residues. The 6-O sulfation of a terminal Gal residue blocks poly-N-acetyllactosamine chain elongation, because the b1-3 GlcNAc-transferase enzyme cannot use sulfated Gal as acceptor substrate. Gal 6-O sulfation is mediated by a single enzyme and GlcNAc 6-O sulfation by two enzymes, the intestinal I-GlcNAc6ST (CHST2) and the corneal C-GlcNAc6ST (CHST6)sulfotransferases. Deficiency of the corneal C-GlcNAc6ST activity causes macular corneal dystrophy as mentioned above.

FIG: KS ELONGATION

Most keratan sulfate carrying proteoglycans are secreted in the interstitial space and are important for the fibrillar organization of collagen fibers. In the cornea, keratan sulfate proteoglycans maintain collagen fibers aligned, which is essential to preserve transparency. The large proteoglycan aggrecan is mainly found in articular cartilage associated to collagen type II. Proteolysis of aggrecan by ADAMTS4 and ADAMTS5 proteases leads to cartilage degradation and to osteoarthritis.

FIG: KS TABLE