Kinesin: a molecular motor with a spring in its step

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Abstract
A key step in the processive motion of two–headed kinesin along a microtubule is the ‘docking’ of the neck linker that joins each kinesin head to the motor's dimerized coiled–coil neck. This process is similar to the folding of a protein β–hairpin, which starts in a highly mobile unfolded state that has significant entropic elasticity and finishes in a more rigid folded state. We therefore suggest that neck–linker docking is mechanically equivalent to the thermally activated shortening of a spring that has been stretched by an applied load. This critical tension–dependent step utilizes Brownian motion and it immediately follows the binding of ATP, the hydrolysis of which provides the free energy that drives the kinesin cycle. A simple three–state model incorporating neck–linker docking can account quantitatively for both the kinesin force–velocity relation and the unusual tension–dependence of its Michaelis constant. However, we find that the observed randomness of the kinesin motor requires a more detailed four–state model. Monte Carlo simulations of single–molecule stepping with this model illustrate the possibility of sub–8 nm steps, the size of which is predicted to vary linearly with the applied load.