Go Back Recombinant Aggrecan IGD interglobular domain His-tagged

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Aggrecan is a large aggregating proteoglycan of articular cartilage. It is also found in aorta, discs and tendons. The aggrecan core protein consists of 2317 amino acids. Up to 130 glucosaminoglycan chains are attached to the core protein and the total molecular mass can reach 2.2 - 3.0 x 106 Daltons. Within the aggrecan molecule 3 globular domains G1, G2 and G3 can be distinguished. Domains G1 and G2 are connected by a rod-shaped polypeptide called interglobular domain (IGD), while the sequence between domains G2 and G3 contains attachment regions for keratan sulfate and chondroitin sulfate chains. Aggrecan interacts via the G1 domain with hyaluronan and link protein to form large aggregates. Such aggregates can contain up to 50 -100 aggrecan monomers noncovalently bound to a single hyaluronan chain through 2 link proteins. The aggregates form a hydrated gel-like structure, which endowes cartilage with resistibility to compression and deformation. Degradation of aggrecan appears to initiate at the C-terminus. The population of aggrecan molecules without the G3 domain increases with ageing. Isolated aggrecanases cleave aggrecan at 4 sites within the chondroitin sulfate -rich region (sites E1667 - G1668, E1480 - G1481, E1771 - A1772, E1871 - L1872) and 1 site within the interglobular domain (E373 - A374). Cleavage at the latter site had been documented by analysis of cartilage proteoglycan breakdown products in rheumatoid and osteoarthritis. To measure aggrecanase activity, an artificial recombinant protein composed of aggrecan interglobular domain with flanking FLAG-sequence and human immunoglobulin G1 constant region was first used by Hughes et al.