Modeling of Chemomechanical Coupling of Cytoplasmic Dynein Motors

Cytoplasmic dynein homodimer is a motor protein that can step processively on microtubules (MTs) toward the minus end by hydrolyzing ATP molecules. Some dynein motors show a complicated stepping behavior with variable step sizes and having both hand-overhand and inchworm steps, while some mammalian dynein motors show simplistic stepping behavior with a constant step size and having only hand-overhand steps. Here, a model for the chemomechanical coupling of the dynein is presented, based on which an analytical theory is given on the dynamics of the motor. The theoretical results explain consistently and quantitatively the available experimental data on various aspects of the dynamics of dynein with complicated stepping behavior and the dynamics of dynein with simplistic stepping behavior. The very differences in the dynamic behavior between the two motors are due solely to different elastic coefficients of the linkage connecting the two dynein heads, with the dynein motors of the complicated and simplistic stepping behaviors having small and large coefficients, respectively. Moreover, it is analyzed that the ATPase rate of the dynein head with a docked linker being larger than that with an undocked linker is indispensable for the unidirectional motility of the motor, and the small free energy change for the linker docking in the strong MT-binding state facilitates the unidirectional motility.