Force Production by Single Kinesin Motors

Motor proteins such as kinesin, myosin, and polymerase convert chemical energy into work via a reaction cycle that couples nucleotide hydrolysis to displacement. Kinetic rates in the cycle that depend upon load are of interest because they identify transitions where structural changes may occur, in the form of power strokes, translocations, diffusive motions, or the like. By modeling data obtained with a molecular force clamp, we show that kinesin mechanochemistry can be characterized by a simple mechanism involving a thermally-activated transition. The effect of external load is to bias progress through a composite conformational state following ATP binding. This leads naturally to tight coupling, in agreement with experiments, and is consistent with recent results suggesting that ATP binding leads to docking of the kinesin neck linker region. Global fits of the model to velocity data suggest that movement is accomplished through a series of two nonidentical substeps every cycle, each measuring about 4 nm. The model accounts quantitatively for velocity data over a wide range of loads and ATP levels and makes testable predictions. Similar considerations account for kinesin processivity, which is found to obey a load-dependent Michaelis-Menten relationship.