We plan to establish the complete primary structure of the remaining, unfinished portions of 1) type II collagen from human hyaline cartilage, 2) type V collagen from human placentae and 3) the basement membrane-associated type IV and 7S collagens from human placentae, including the amino acid sequence and the post-translational modifications such as hydroxylation of prolyl and lysyl residues and glycosylation of the hydroxylysyl residues. This objective is a part of our long term studies to understand the biochemical and molecular bases for the structural and """"""""nonstructural"""""""" functions of collagens and their alterations and roles in various experimental and human diseases. The foundation for the proposed work has been carefully laid during the past grant periods by isolation and characterization of the genetically distinct types of collagens, and the component CNBr peptides derived from them. The complete amino acid sequence of Alpha 1(I), Alpha2 and Alpha1(III) has now been established. The sequence analysis of Alpha1(V) is approximately 40% completed (Alpha1(V)-CB1, 4 and 7 and most of CB5), and that for Alpha 2 (V) is approximately 10% completed (Alpha2(V)-CB5 and most of CB4). The Alpha1(IV) chain is also approximately 30% completed (Alpha 1 (IV)-CB2,3,4,5 and 9 and partial sequences of CB6, 7 and 8). The work on Alpha2(IV), Alpha1(II) and 7S has been initiated. Collagen is the most ubiquitouxly distributed protein in the human body, and plays a critical role in the maintenance of the architectural integrity and function of organs. It is intimately involved in various physiologival processes such as m orphogenesis and tissue remodeling. It is also involved in a vaiety of pathologic states, some acquired and others inherited. It is also becoming increasingly clear that collagen and collagen-derived products exert important biologic effects on various cells involved in inflammation; e.g., platelets, macrophages and fibroblasts. Detailed information on the primary structure of this family of proteins is, therefore, essential to our understanding of its biologic properties and behavior.
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