Myosin Molecular Motors
Dr. Warshaw received his Ph.D. in Physiology and Biophysics at the University of Vermont in 1978, and continued his research studying the molecular mechanism of muscle contraction as a post-doctoral associate at the University of Massachusetts Medical School. He returned to the University of Vermont as an Assistant Professor of Molecular Physiology & Biophysics in 1983 and now is Professor and Chair of the Department. Currently, Dr. Warshaw's lab is using state-of-the-art single molecule detection and manipulation techniques to characterize the structure and function of myosin molecular motors in normal and disease states of the cardiovascular system.
The myosin superfamily now consists of at least 18 different classes of myosin molecular motors. These myosins interact with actin to generate force and motion that is used in a range of biological functions from muscle contraction, organelle transport, to cell division. All myosins share significant structural and functional capacities, i.e. they possess a motor domain that hydrolyzes ATP, binds actin, and is the force and motion generator. From the motor domain, a light-chain and/or calmodulin-binding domain emerges that acts like a mechanical lever to amplify small conformational changes that occur within the motor domain. The differences in both structure and function among the various myosins can provide a model system to help probe the molecular structure and function of myosin as a chemomechanical enzyme. For example, we are characterizing the molecular biophysics of myosin V, a double-headed specie, which is believed to be a vesicular transporter. This myosin has been shown to be both processive and takes large, ~40nm steps. To be processive, both heads should have a high duty ratio and be coordinated, so that forward motion can occur and that at least one head is attached to its actin track at any time to prevent the myosin and its cargo from diffusing away. Using the laser trap and single molecule fluorescence detection techniques, questions regarding the coordination between heads, what structural feature of the myosin V molecule is necessary for processivity, and how strain between the heads serves as a coordinating signal are being addressed.
Sckolnick M, Krementsova EB, Warshaw DM, Trybus KM (2013) More than just a cargo adapter, melanophilin prolongs and slows processive runs of myosin Va. J Biol Chem 288(41): 29313-22.
Michalek AJ, Howarth JW, Gulick J, Previs MJ, Robbins J, Rosevear PR, Warshaw DM (2013) Phosphorylation modulates the mechanical stability of the cardiac myosin-binding protein C motif. Biophys J 104(2): 442-52.
Ali MY, Previs SB, Trybus KM, Sweeney HL, Warshaw DM (2013) Myosin VI has a one track mind versus myosin Va when moving on actin bundles or at an intersection. Traffic 14(1): 70-81.
Zhang C, Ali MY, Warshaw DM, Kad NM (2012) A branched kinetic scheme describes the mechanochemical coupling of Myosin Va processivity in response to substrate. Biophys J 103(4): 728-37.
Walcott S, Warshaw DM, Debold EP (2012) Mechanical coupling between myosin molecules causes differences between ensemble and single-molecule measurements. Biophys J 103(3): 501-10.
Previs MJ, Beck Previs S, Gulick J, Robbins J, Warshaw DM (2012) Molecular mechanics of cardiac myosin-binding protein C in native thick filaments. Science 337(6099): 1215-8.
Moore JR, Leinwand L, Warshaw DM (2012) Understanding cardiomyopathy phenotypes based on the functional impact of mutations in the myosin motor. Circ Res 111(3): 375-85.
Professor and Chair
Department of Molecular Physiology & Biophysics
Office: HSRF 116
Lab: HSRF 115
- 12/17/2013 11:30 AM - 12:30 PM
- 1/28/2014 11:30 AM - 12:30 PM
- 2/4/2014 11:30 AM - 12:30 PM
Dr. Andrew McKenzie
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