| ||Address: ||McCallum Basic Health Sciences Building |
1918 University Blvd.
Birmingham, AL 35294-0005
Lab Research Focus: Cardiac Muscle Proteins, Molecular Motors, and Fluorescence Spectroscopy
The research in my laboratory is focused on (1) the mechanisms of two linear molecular motors, myosin and kinesin, and (2) the mechanisms of activation and regulation of cardiac muscle. These studies are carried out using a combination of biophysical and molecular biological approaches.
Molecular Motors. The linear molecular motors are ATPases which “walk” on microfilaments unidirectionally. Kinesin moves organelles along microtubules in diverse systems, and in muscle myosin moves along the actin filament. The myosin-actin interaction ultimately results in muscular contraction. The energy for these mechanical movements is derived from the hydrolysis of ATP. We are interested in studying the reversible structural alterations in the two motors that occur during ATP hydrolysis and understanding the structural basis of the actions of the motor proteins.
Calcium Activation. The myosin-actin interaction is activated by calcium binding to one subunit (troponin C) of the protein troponin, which is bound to the actin filament. Elucidation of the calcium activation mechanism requires an understanding of the mechanism of calcium binding to troponin and the global structural changes induced by calcium in all three troponin subunits and in another regulatory protein, tropomyosin. We have recently elucidated the kinetic mechanism of calcium binding to troponin from cardiac muscle and will extend this study of calcium binding to the thin filament (i.e., actin filament decorated with both troponin and tropomyosin). A complete kinetic mechanism is needed for the understanding of calcium-induced structural changes in these proteins. The kinetic studies are being pursued in the presteady state using rapid mixing stopped flow and the structural studies are performed by a variety of fluorescence methods that are extensively used in this laboratory, and complemented by collaborative studies using NMR. To complement these solution studies, we have recently initiated a project on the mechanics of muscle fibers in which contractile force is measured simultaneously with measurements of fluorescence signal to allow a closer and more direct examination of structural changes on proteins that occur resulting from contraction. This is a unique and novel approach to the understanding of the contractile mechanism at the molecular level.
Herbert C. Cheung (b. 1933) completed undergraduate training at Rutgers University (A.B. with honors, 1954) and did graduate work in physical chemistry and physics at Cornell University (M.S., 1956) and Rutgers University (Ph.D., 1961). Dr. Cheung came to UAB in 1969 as Associate Professor in Engineering Biophysics. In 1974, he became Professor of Biophysics, and in 1982 he became Professor of Biochemistry and Molecular Genetics. He currently serves on the Editorial Board of the Journal of Fluorescence and a second 4-year term on the Physical Biochemistry Study Section at the National Institutes of Health. Dr. Cheung’s research is supported by grants from NIH.