Manipulating a Molecular Motor by Changing Substrate and Inhibitor Selectivity
Peter G. Gillespie*
Oregon Hearing Research Center & Vollum Institute,
Oregon Health Sciences University,
Portland, OR 97201 USA
This is an abstract
for a presentation given at the
Eighth
Foresight Conference on Molecular Nanotechnology.
There will be a link from here to the full article when it is
available on the web.
Experimental alteration of molecular motors to use different fuel sources, allow coupling to nonnative partners, or permit precise control with pharmacological means will have significant impact on many biological fields, as well as on nanotechnology. We are interested in proving whether the molecular motor myosin I-beta participates in adaptation of mechanical transduction by hair cells, the sensory cells of the inner ear. Because we intended to acutely inhibit the activity of myosin I-beta during a physiological recording, we designed a mutation in the molecule (Y61G) that rendered it sensitive to inhibitors that otherwise had no effect on adaptation. Y61G myosin I-beta hydrolyzes ATP normally, although it moves along actin filaments about three times faster than does the wild-type myosin I-beta. N6(2-methylbutyl) ADP blocks the ATPase activity and motility of Y61G myosin I-beta at far lower concentrations than it blocks the wild-type myosin. Hair cells expressing Y61G myosin I-beta now exhibit a N6(2-methylbutyl) ADP block of adaptation, suggesting that myosin I-beta is a critical player in hair-cell adaptation. Our strategy has broader applications; we can apply this mutant-inhibitor strategy to many other motors, as well as other enzymes. In addition, we can conceivably change myosin I-beta or another motor to use a completely different fuel source or carry out other nonnative functions.
*Corresponding Address:
Peter G. Gillespie
Oregon Hearing Research Center & Vollum Institute
Oregon Health Sciences University
Portland, OR 97201 USA
Email: [email protected]
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