The long term objective is to provide a better understanding of the structure, biochemical properties and biologic functions of selected macromolecules which are important components of developing epiphyseal cartilage and growth plate cartilage. A major goal is to define the relation between the structure and functional properties of the link proteins. The normal structure and special properties of developing epiphyseal and growth plate cartilage depend upon the formation of extremely large, stable proteoglycan aggregates in extracellular matrix. Link proteins stabilize the binding of proteoglycan monomers to hyaluronate in these aggregates. One objective of the proposed studies is to conclusively demonstrate that the link proteins also increase aggregate size. Two forms of link proteins, with molecular weights of 46K and 51K, are present in proteoglycan aggregates. We have recently developed a method involving lectin affinity chromatography to isolate the individual link proteins on a preparative scale. Our recent studies suggest that the 51K link protein selectively increases aggregate size, while the 46K link protein seems to be required to effectively stabilize the binding of proteoglycan monomers to hyaluronate. A second objective is to establish the selective effects of the individual link proteins on aggregate size and stability by sedimentation velocity and electron microscopic studies of aggregates reassembled in the presence or absence of the 46K and 51K link proteins. A third objective is to elucidate the biochemical mechanism by which the link proteins increase aggregate size and stabilize aggregate. Studies will be carried out to examine the capacity of the individual link proteins to bind to hyaluronate, and to the hyaluronic acid binding region of proteoglycan monomer core protein. The structural features of the individual link proteins which mediate this binding, underlie their capacity to increase aggregate size, and stabilize the binding of proteoglycan monomers to hyaluronic acid will be examined.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Method to Extend Research in Time (MERIT) Award (R37)
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Montefiore Medical Center (Bronx, NY)
New York
United States
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