Yount, Ralph

Research

Professor Yount received his graduate training in biochemistry /chemistry under D. E. Metzler at Iowa State University and did postdoctoral work with D. E. Koshland, Jr. at Brookhaven National Laboratory. He is a past editorial board member and a member of the publications committee for the Journal of Biological Chemistry.

He served as vice-president and was chairman of the postdoctoral fellowship committee for the Muscular Dystrophy Association for 15 years. He is a former study section member on Committee A of the National Heart, Lung, and Blood Institute and was on the Biochemistry/Biophysics panel for NSF for three years. He is a past chairman of the Muscle Proteins Gordon Conference and member of the National Council of the Biophysical Society. In 1986 he received a MERIT award from the National Institutes of Health for long-term funding of his research on muscle. He is a past president of the Biophysical Society in 1994/95 and served as president of the Federation of American Societies for Experimental Biology (FASEB) in 1997/98. He was on the Board of Scientific Counselors of the National Institute of Arthritis and Musculoskeletal and Skin Diseases. His research was funded by NIH for 43 consecutive years.

Professor Yount’s primary interests are in the molecular mechanism of muscle contraction and of motility in biological systems. His group prepares new analogs of ATP to be used as monitors of contractile events and/or as probes of the molecular structure of contractile proteins. Some recent derivatives contain stable free radicals (spin probes) or fluorescent/luminescent probes attached to ATP or ATP-like molecules that also contain photo reactive groups capable of forming covalent bonds to proteins upon irradiation of the appropriate complexes. These probes are then covalently bound near the ATP-binding site and have been found not to interfere with contractile events. We “trap” the ADP product of hydrolysis of these ATP-like molecules at the active site of myosin (the major contractile protein in muscle) with transition state analogs of inorganic phosphate, e.g., vanadate or AlF4. Extraneous ADP analog is removed by washing and myosin then photo labeled specifically in a benign manner. Thus it is possible for the first time to introduce EPR or fluorescent/luminescent reporter groups onto the “heads” of myosin in a specific manner even in complex muscle fibers. This approach allows us to monitor the movement of the heads during the contractile cycle. Other studies are aimed at using these new derivatives to reveal the nature of force generation by kinesin and kinesin-like molecules that move on tracks of microtubules.

Publications

• Lawson JD, Pate E, Rayment I, Yount RG. “Molecular Dynamics Analysis of Structural Factors influencing Back Door Pi release in Myosin”, Biophys J. 2004 86:3794-803
• Wang D, Luo Y, Cooke R, Grammer J, Pate E, Yount RG,“Synthesis of a spin-labeled photoaffinity ATP analogue, and its use to specifically photolabel myosin cross-bridges in skeletal muscle fibers”, J Muscle Res Cell Motil. 1999 :743-53
• Chen X, Siems WF, Asbury GR, Yount RG, “Fingerprint patterns from laser-induced azido photochemistry of spin-labeled photoaffinity ATP analogs in matrix-assisted laser desorption/ionization mass spectrometry”, J Am Soc Mass Spectrom. 1999 12 1337-40
• Gulick AM, Bauer CB, Thoden JB, Pate E, Yount RG,“Rayment X-ray structures of the Dictyostelium discoideum myosin motor domain with six non-nucleotide analogs”, J Biol Chem. 2000 275:398-408
• Chen X, Grammer J, Cooke R, Pate E, Yount RG, “Synthesis and Characterization of Novel Spin-Labeled Photoaffinity Nonnucleoside Analogues of ATP as Structural and EPR Probes for Myosin”, Bioconjug Chem. 2000 11:725-733.4
• Chen, X, Grammer, J, Lawson, JD, Cooke, R, Pate, E, Yount RG, “A Novel Restricted Photoaffinity Spin-Labeled Non-Nucleoside ATP Analogue as a Covalently Attached Reporter Group of the Active Site of Myosin”, Biochemistry 41, 2609-2620 (2002)
• Naber,N, Minehardt,T. Rice,S, Chen, X., Grammer,J., Matuska,M., Vale, R, Kollman, P., Car, R. Yount, RG,., Cooke,R. Pate, E., “Closing of the Nucleotide Pocket of Kinesin-Family Motors upon Binding to Microtubules”, Science,300,798-801(2003)