MOLECULAR-CLONING AND ANALYSIS OF THE PROTEIN MODULES OF AGGRECANS

The large aggregating chondroitin sulfate proteoglycan of cartilage, a ggrecan, has served as a prototype of proteoglycan structure. Molecula r cloning has elucidated its primary structure and revealed both known and unknown domains. To date the complete structures of chicken, rat and human aggrecans have been deduced, while partial sequences have be en reported for bovine aggrecan. A related proteoglycan, human versica n, has also been cloned and sequenced. Both aggrecan and versican have two lectin domains, one at the amino-terminus which binds hyaluronic acid and one at the carboxyl-terminus whose physiological ligand is un known. Both lectins have homologous counterparts in other types of pro teins. Within the aggrecans the keratan sulfate domain may be variably present and also has a prominent repeat in some species. The chondroi tin sulfate domain has three distinct regions which vary in their prom inence in different species. The complex molecular structure of aggrec ans is consistent with the concept of exon shuffling and aggrecans ser ve as suitable prototypes for comprehending the evolution of multi-dom ain proteins.