Studies outlined in this proposal are directed towards an understanding of the structural assembly of muscle and the molecular basis of muscle contraction. Proposed work includes (1) Preparation of true crystals of a large helical fragment of the myosin molecule. This study is designed to try to learn more about the three-dimensional architecture of the contractile proteins. (2) Studies on the structure of the thick filaments of muscle. We have studied and propose to study further here several unusual aggregates of myosin and its fragments in order to learn more about the packing arrangements of myosin filaments and the factors which influence their geometry. (3) Studies on the biosynthesis of myosin and its assembly to form the thick filament. Several lines of evidence suggest that it may be that the myosin molecule is synthesized in embryo as an inactive precursor of the adult protein. Cell-free protein synthetic systems are being used to examine this possibility. Moreover, studies in the muscle cells in culture are proposed in order to examine the kinetics of synthesis of myosin and its several subunits during embryonic development. (4) Studies on the amino acid sequence of the helical rod portion of myosin have been initiated to try to understand the molecular arrangement of the subunit polypeptide chains of myosin and to build plausible models for its structure. Bibliographic references: Wagner, H., Jr., Smith, T. W., Young, M., "Resistance of Active Monovalent Cation Transport to Pronase Digestion of Intact Human Erythrocytes", Arch. Biochem. Biophys. 163:95, 1974. Smith, T. W., Wagner, H., Jr., and Young, M., "Cardiac Glycoside Interaction with Solubilized Myocardial Sodium- and Potassium- Dependent Adenosine Triphosphatase", Mol. Pharmacol. 10:626, 1974.