This grant will support research in two areas: molecular immunology and lipoprotein biochemistry. The common thread is our interest in the structure and dynamics of functional macromolecular complexes, particularly complexes formed between antibodies, antigens, complement and receptors, and also in complexes formed between proteins and lipids. The goal of the molecular immunology projects include elucidation of (i) the mechanisms by which antibody, through interaction with antigen, activates complement, (ii) the relationship between their structures and the dynamical properties of antibodies, and (iii) the ultrastructures of the complexes formed between antibodies and cellular receptors. The goals of the lipoprotein projects include elucidation of (i) the configuration of apoprotein B on the surface of the low density lipoproteins (LDL), (ii) the structural changes which ensue when very low density lipoproteins (VLDL) are catabolized by the lipoprotein lipases, and (iii) the changes in chylomicron structure which occur when temperature is lowered. The methodology to be utilized includes ultracentrifugation, diffusion, quasielastic light scattering, circular dichroism, stopped-flow fluorescence, time-resolved fluorescence depolarization, and electron microscopy. These projects are related to problems of health; thus, (i) the triggering of complement and cells by immune complexes and antigens is a critical feature of the immune defense, and (ii) high concentrations of chylomicron and VLDL 'remnants' remaining after lipolysis, and of LDL are closely associated with the development of tha atherosclerotic lesion, and associated heart attack, senility and stroke.
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