Dynamics of dimeric kinesins: Limping, effect of longitudinal force, effects of neck linker extension and mutation, and comparison between kinesin-1 and kinesin-2

Abstract

Conventional kinesin (kinesin-1) can walk on microtubule filaments in an asymmetric hand-over-hand manner, exhibiting a marked alternation in the mean dwell time in successive steps. Here, we study computationally the asymmetric stepping dynamics of the kinesin-1 homodimer, revealing its origin and providing quantitative explanations of the available experimental data. The alternation in the mean dwell time in successive steps arises from the alternation in the mechanochemical coupling ratio, which is in turn caused by the alternation in the slight variation of the stretched neck linker length. Both the vertical and backward longitudinal forces can enhance the asymmetric ratio. Additionally, other aspects of the stepping dynamics of the dimer such as the velocity versus longitudinal force, extended neck linker, etc., are also studied. In particular, the conflicting experimental data, with some showing that the velocity does not change with the forward longitudinal load while others showing that the velocity increases largely with the forward longitudinal load, are explained quantitatively and consistently. The intriguing experimental data showing that cysteine-light Drosophila and human kinesin-1 mutants have different load-dependent velocity from the wild-type cases as well as that kinesin-2 dimers have different load-dependent velocity from the kinesin-1 are also explained consistently and quantitatively.