Ronald S Rock
Research Summary / Selected Publications
An important property of living organisms is their ability to move when needed. All such directed movements, including intracellular trafficking, cell division, and muscle contraction, are driven by a set of molecular machines that are only a few nanometers in diameter. We would like to understand how one of these motors, myosin, couples ATP hydrolysis into motility along actin filaments, and how it has been tuned for a wide variety of tasks in the cell.
While stepping, myosin travels through a specific sequence of tightly coupled biochemical and mechanical states. Without such coordination, structural transitions would occur at improper times and the motor would not function. Our challenge is to unravel the coordination mechanisms in these motors. We focus on the unconventional myosins, including myosin V, VI, and X. These motors drive several forms of cargo transport and play key roles in the organization of actin-based structures. Unlike myosin II, which operates in large ensembles to drive high-speed motility in muscle, these unconventional myosins operate in smaller numbers and thus have different mechanical and kinetic properties.
We primarily use single-molecule techniques to study motility, including optical tweezers to measure forces and single fluorophore imaging to follow biochemical events. These methods allow us to probe the protein motions in a manner that is unobscured by other motor molecules, which may or may not be acting in concert.
An important property of living organisms is their ability to move when needed. All such directed movements, including intracellular trafficking, cell division, and muscle contraction, are driven by a set of molecular machines that are only a few nanometers in diameter. We would like to understand how one of these motors, myosin, couples ATP hydrolysis into motility along actin filaments, and how it has been tuned for a wide variety of tasks in the cell.
While stepping, myosin travels through a specific sequence of tightly coupled biochemical and mechanical states. Without such coordination, structural transitions would occur at improper times and the motor would not function. Our challenge is to unravel the coordination mechanisms in these motors. We focus on the unconventional myosins, including myosin V, VI, and X. These motors drive several forms of cargo transport and play key roles in the organization of actin-based structures. Unlike myosin II, which operates in large ensembles to drive high-speed motility in muscle, these unconventional myosins operate in smaller numbers and thus have different mechanical and kinetic properties.
We primarily use single-molecule techniques to study motility, including optical tweezers to measure forces and single fluorophore imaging to follow biochemical events. These...
Nagy, S., Ricca, B.L., Norstrom, M., Courson, D.S., Brawley, C.M., Smithback, P., Rock, R.S. (2008) "A myosin motor that selects bundled actin for motility." Proc. Natl. Acad. Sci. USA 105: 9616-20. PubMed
Rizvi, S.A.; Courson, D.S.; Keller, V.A.; Rock, R.S.; Kozmin, S.A. (2008) The dual mode of action of bistramide A entails severing of filamentous actin and covalent protein modification. Proc. Natl. Acad. Sci. USA 105: 4088-92. PubMed
Rock, R. S., Ramamurthy, B., Dunn, A. R., Beccafico, S., Rami, B. R., Morris, C., Spink, B. J., Franzini-Armstrong, C., Spudich, J. A. and Sweeney, H. L. (2005). "A Flexible Domain Is Essential for the Large Step Size and Processivity of Myosin VI." Mol Cell 17: 603-9. PubMed
Churchman, L. S., Okten, Z., Rock, R. S., Dawson, J. F. and Spudich, J. A. (2005). "Single molecule high-resolution colocalization of Cy3 and Cy5 attached to macromolecules measures intramolecular distances through time." Proc Natl Acad Sci U S A 102: 1419-23. PubMed
Okten, Z., Churchman, L. S., Rock, R. S. and Spudich, J. A. (2004). "Myosin VI walks hand-over-hand along actin." Nat Struct Mol Biol 11: 884-7. PubMed
Rock, R. S., Rice, S. E., Wells, A. L., Purcell, T. J., Spudich, J. A. and Sweeney, H. L. (2001). "Myosin VI is a processive motor with a large step size." Proc Natl Acad Sci U S A 98: 13655-9.
PubMed
Murphy, C. T., Rock, R. S. and Spudich, J. A. (2001). "A myosin II mutation uncouples ATPase activity from motility and shortens step size." Nat Cell Biol 3: 311-5.
PubMed
Rock, R. S., Rief, M., Mehta, A. D. and Spudich, J. A. (2000). "In vitro assays of processive myosin motors." Methods 22: 373-81.
PubMed
Rief, M., Rock, R. S., Mehta, A. D., Mooseker, M. S., Cheney, R. E. and Spudich, J. A. (2000). "Myosin-V stepping kinetics: a molecular model for processivity." Proc Natl Acad Sci U S A 97: 9482-6.
PubMed
Mehta, A. D., Rock, R. S., Rief, M., Spudich, J. A., Mooseker, M. S. and Cheney, R. E. (1999). "Myosin-V is a processive actin-based motor." Nature 400: 590-3.
PubMed
Nagy, S., Ricca, B.L., Norstrom, M., Courson, D.S., Brawley, C.M., Smithback, P., Rock, R.S. (2008) "A myosin motor that selects bundled actin for motility." Proc. Natl. Acad. Sci. USA 105: 9616-20. PubMed
Rizvi, S.A.; Courson, D.S.; Keller, V.A.; Rock, R.S.; Kozmin, S.A. (2008) The dual mode of action of bistramide A entails severing of filamentous actin and covalent protein modification. Proc. Natl. Acad. Sci. USA 105: 4088-92. PubMed
Rock, R. S., Ramamurthy, B., Dunn, A. R., Beccafico, S., Rami, B. R., Morris, C., Spink, B. J., Franzini-Armstrong, C., Spudich, J. A. and Sweeney, H. L. (2005). "A Flexible Domain Is Essential for the Large Step Size and Processivity of Myosin VI." Mol Cell 17: 603-9. PubMed
Churchman, L. S., Okten, Z., Rock, R. S., Dawson, J. F. and Spudich, J. A. (2005). "Single molecule high-resolution colocalization of Cy3 and Cy5 attached to macromolecules measures intramolecular distances through time." Proc Natl Acad Sci U S A 102: 1419-23. PubMed
Okten, Z., Churchman, L. S., Rock, R. S. and Spudich, J. A. (2004). "Myosin VI walks hand-over-hand along actin." Nat Struct Mol Biol 11: 884-7. PubMed
