Understanding how any motor works requires specifying the motor's mechanical components and determining how these components move and interact during the force-generating process. The internal workings of motor proteins, which power muscle contraction, propel swimming sperm, and carry organelles along tracks in cells, are not understood. This proposal intends to reveal the mechanical elastic components of the motor protein kinesin.
The specific aims are: to measure the elasticity of kinesin under (1) torsional, (2) longitudinal, and (3) extensional forces, to locate the corresponding molecular compliant elements, and to evaluate the impact of these external forces on kinesin force generation. Optical tweezers and calibrated force fibers will be used to measure force and displacement of single-molecules for the characterization of motor elastic properties. Recombinant protein expression techniques will be utilized to identify the elastic components. The information obtained in this proposal can be used to develop a model for operation of the kinesin machine.
| Schief, William R; Clark, Rutilio H; Crevenna, Alvaro H et al. (2004) Inhibition of kinesin motility by ADP and phosphate supports a hand-over-hand mechanism. Proc Natl Acad Sci U S A 101:1183-8 |
| Bradley, Philip; Chivian, Dylan; Meiler, Jens et al. (2003) Rosetta predictions in CASP5: successes, failures, and prospects for complete automation. Proteins 53 Suppl 6:457-68 |
