Donald A. Winkelmann
Robert Wood Johnson Medical School
Department of Pathology & Laboratory Medicine
Piscataway, NJ 08854
Protein structure, molecular motors, protein engineering, macromolecular assembly, muscle contraction
The 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.