Force Generation in Kinesin Hinges on Cover-​Neck Bundle Formation

Summary: In kinesin motors, a fundamental question concerns the mechanism by which ATP binding generates the force required for walking. Anal. of available structures combined with mol. dynamics simulations demonstrates that the conformational change of the neck linker involves the nine-​residue-​long N-​terminal region, the cover strand, as an element that is essential for force generation. Upon ATP binding, it forms a β sheet with the neck linker, the cover-​neck bundle, which induces the forward motion of the neck linker, followed by a latch-​type binding to the motor head. The estd. stall force and anisotropic response to external loads calcd. from the model agree with force-​clamp measurements. The proposed mechanism for force generation by the cover-​neck bundle formation appears to apply to several kinesin families. It also elucidates the design principle of kinesin as the smallest known processive motor.