Kinesin: a molecular motor with a spring in its step.
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 beta-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.
Thomas
Neil
N
Department of Biology, Graduate School of Sciences, Kyushu University, Fukuoka 812-8581, Japan. n.thomas@bham.ac.uk
Imafuku
Yasuhiro
Y
Kamiya
Tsutomu
T
Tawada
Katsuhisa
K
D000255:Adenosine Triphosphate / Q000378:metabolism; D006868:Hydrolysis; D016547:Kinesins / Q000737:chemistry / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D020409:Molecular Motor Proteins / Q000737:chemistry / Q000378:metabolism*; D017510:Protein Folding
D020409:Molecular Motor Proteins; D000255:Adenosine Triphosphate; D016547:Kinesins