Aggrecanase Explained

Aggrecanases are extracellular proteolytic enzymes that are members of the ADAMTS (A Disintegrin And Metalloprotease with Thrombospondin Motifs) family. Aggrecanases act on large proteoglycans known as aggrecans, which are components of connective tissues such as cartilage. The inappropriate activity of aggrecanase is a mechanism by which cartilage degradation occurs in diseases such as arthritis. At least two forms of aggrecanase exist in humans: ADAMTS4 or aggrecanase-1^[1] and ADAMTS5 or aggrecanase-2.^[2] Both proteins contain thrombospondin (TS) motifs required for proper recognition of substrates.^[3] Although both proteins can cleave the substrate aggrecan at the same position, they differ in kinetics and in secondary cleavage sites.^[4]

Notes and References

1. 10.1126/science.284.5420.1664 . Tortorella . MD . Burn . 1999 . TC . Pratta . MA . Abbaszade . I . Hollis . JM . Liu . R . Rosenfeld . SA . Copeland . RA . Decicco . CP . 8. Purification and cloning of aggrecanase-1: a member of the ADAMTS family of proteins . Science . 284 . 5420. 1664–6 . 10356395 . 1999Sci...284.1664T .
2. 10.1074/jbc.274.33.23443 . Abbaszade . I . Liu . 1999 . RQ . Yang . F . Rosenfeld . SA . Ross . OH . Link . JR . Ellis . DM . Tortorella . MD . Pratta . MA . 8. Cloning and characterization of ADAMTS11, an aggrecanase from the ADAMTS family . J Biol Chem . 274 . 33. 23443–50 . 10438522 . free .
3. Tortorella . M . Pratta . M . Liu . RQ . Abbaszade . I . Ross . H . Burn . T . Arner . E. . 2000 . The thrombospondin motif of aggrecanase-1 (ADAMTS-4) is critical for aggrecan substrate recognition and cleavage . J Biol Chem . 275 . 33. 25791–7 . 10827174 . 10.1074/jbc.M001065200 . free .
4. 10.1016/S0945-053X(02)00069-0 . Tortorella . MD . Liu . RQ . Burn . T . Newton . RC . Arner . E. . 2002 . Characterization of human aggrecanase 2 (ADAM-TS5) substrate specificity studies and comparison with aggrecanase 1 (ADAM-TS4) . Matrix Biol . 21 . 6. 499–511 . 12392761 .