MECHANISM AND REGULATION OF CONTRACTILE PROTEINS

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The long term goal of this research is to develop a better understanding of the mechanisms underlying contractile processes and their regulation. Contractility is an important property of many biological systems in addition to that of skeletal muscle. The smooth muscles in the gastro-intestinal tract provide the agitation necessary for proper digestion and the smooth muscles in the circulatory system play a major role. Contractile proteins in non-muscle cells are believed to be involved in cell division, cytoplasmic streaming, phagocytosis and other processes requiring modification and maintenance of cell shape. The contraction of the platelet cell is important in the maturation of blood clots. This project is directed along several major lines. The first involves development of a better understanding of the skeletal muscle system. This muscle is the best understood contractile system, but much remains to be determined including the influence of the filamentous organization and the detailed nature and control of the interaction between actin and myosin. A second major line of research involves the application to other contractile systems of the techniques developed with skeletal muscle. The smooth muscle of chicken gizzard will be initially studied. Other possible applications include the non-muscle contractile system of platelets. The third major line of research is the use of the contractile proteins as a model system for developing a general understanding of the influence on enzymatic catalysis and regulation of having enzyme sites supramolecular structures. This is a problem which is central to the extension of enzymology from the study of reactions in dilute solutions in vitro into the complexity of reactions as they occur in vivo. Extensive use will be made of the exchange reaction of isotopically labeled oxygen atoms between water and the phosphate produced by ATP hydrolysis. Analysis of this exchange reaction has provided powerful insight into the mechanism of skeletal myosin and continue to do so. It represents a convenient and promising probe into the mechanisms of other contractile systems as well.