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Protein structure. molecular motors. protein engineering. macromolecular assembly. muscle contractionThe focus of our research is the study of macromolecular structure and assembly with our efforts concentrated on the analysis of the protein myosin and its interaction with actin. Actin and myosin are highly conserved proteins that participate in determination of cell shape. cellular motility. cytokinesis and contractility. Our research uses the techniques of protein biochemistry. molecular genetics. immunochemistry. electron microscopy and crystallography to analyze myosin structure. assembly and function. These studies have contributed to the current understanding of myosin structure and have culminated in the determination of the structure of the myosin motor domain at 2.8 Å resolution. The molecular model of myosin is revealing exciting new insights into the fundamental mechanism of biological energy transformation. These structural studies are complemented by the use of molecular genetics and site directed mutagenesis of cloned myosin genes. In addition to its role in generating force and motion in all eukaryotic cells. myosin is a major structural component of the contractile organelle of muscle and non-muscle cells. We are investigating this role by expression of GFP-myosin chimeras and fluorescent microscopy of living cardiac and skeletal muscle cells. Selected PublicationsSrikakulam R, Liu L, Winkelmann DA. (2008) Unc45b forms a cytosolic complex with Hsp90 and targets the unfolded myosin motor domain. PLoS ONE. 3(5):e2137. Liu L, Srikakulam R, Winkelmann DA. (2008) Unc45 activates Hsp90-dependent folding of the myosin motor domain. J Biol Chem. 283(19):13185-93. Srikakulam. R. and Winkelmann. DA. (2004). Chaperone-mediated folding and assembly of myosin in striated muscle J. Cell Science. 117:641-652. Wang. Q.. Moncman. CL and Winkelmann. DA. (2003). Mutations in the motor domain modulate myosin activity and myofibril organization. J. Cell Science 116:4227-4238. Chow. D.. Srikakulam. R. Chen. YR and D.A. Winkelmann. DA. (2002). Folding of the striated muscle myosin motor domain. J. Biol. Chem. 277:36799-36807. Xiang. X.. G. Han. D.A. Winkelmann. W. Zuo and N.R. Morris. (2000) Dynamics of cytoplasmic dynein in living cells and the effect of a mutation in the dynactin complex actin-related protein Arp1. Current Biology 10: 603-606. Srikakulam. R. and Winkelmann. D.A. (1999) Myosin II folding is mediated by a molecular chaperonin. J. Biol. Chem. 274:27265-27273. Colognato. H.. D.A. Winkelmann and P.D. Yurchenco. (1999) Laminin polymerization induces a receptor-cytoskeleton network. J. Cell Biol. 145:619-631. Riveline. D.. A. Ott. F. Julicher. D.A. Winkelmann. O. Cardoso. J-J. Lacapere. S. Magnusfottir. J-L. Viovy. L. Gorre-Talini and J. Prost. (1998) Acting on actin: The electric motility assay. Eur. J. Biophys. 27:403-408. |
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