Structural changes in the neck linker of kinesin explain the load dependence of the motor's mechanical cycle

The two-headed motor protein kinesin hydrolyzes ATP and moves on microtubul e tracks towards the plus end. The motor develops speeds and forces of the order of hundreds of nanometers per second and piconewtons, respectively. R ecently, the dependence of the velocity, the dissociation rate and the disp lacement variance on the load and the ATP concentration were measured in vi tro for individual kinesin molecules (Coppin et at, 1997; Visscher et al., 1999) over a wide range of forces. The structural changes in the kinesin mo tor that drive motility were discovered by Rice et al. (1999). Here we pres ent a phenomenological model for force generation in kinesin based on the h i-stable, nucleotide-dependent behavior of the neck linker. We demonstrate that the model explains the mechanical,kinetic and statistical (experimenta l) data of Coppin et al. (1997). We also discuss the relationship between t he model results and experimental data of Visscher et al. (1999). (C) 2001 Academic Press.