Interaction between motor domains can explain the complex dynamics of heterodimeric kinesins

Motor proteins are active enzyme molecules that play a crucial role in many biological processes. They transform chemical energy into mechanical work and move unidirectionally along rigid cytoskeleton filaments. Single-molecule experiments indicate that motor proteins, consisting of two motor domains, move in a hand-over-hand mechanism where each subunit changes between trailing and leading positions in alternating steps, and it is assumed that these subunits do not interact with each other. However, recent experiments on heterodimeric kinesins suggest that the motion of motor domains is not independent, but rather strongly coupled and coordinated, although the mechanism of these interactions is not known. We propose a simple discrete stochastic model to describe the dynamics of homodimeric and heterodimeric two-headed motor proteins. It is argued that interactions between motor domains modify original free energy landscapes for each motor subunit, while motor proteins still move via the hand-over-hand mechanism but with different transition rates specified by the new free energy profiles. Our calculations of biophysical properties agree with experimental observations. Several ways to test the theoretical model are proposed.

Figure 1

(Color online) General schematic view of discrete stochastic models for kinesins. W-W labels the homodimeric motor protein with both wild-type motor heads, M-M corresponds to the homodimeric kinesins with mutations in both motor domains, while W-M describes the heterodimeric motor proteins with mutation in only one of the heads. The parameters $\epsilon$, ${\epsilon }_1$, and ${\epsilon }_2$ describe free energy changes due to mutations relative to the wild-type motor proteins.

Figure 2

(Color online) (a) Force-velocity curves for W-W homodimeric kinesins (solid line) and for W-M heterodimeric kinesins (dashed line) at $\left[\text{ATP}\right]=1\text{m}M$. Symbols correspond to experimental measurements from Ref. [14]. (b) Velocities of W-W homodimeric kinesins (solid line) and W-M heterodimeric kinesins (dashed line) as a function of [ATP] at the constant external force $F=0.5\text{pN}$. The velocity of homodimeric M-M kinesins is zero at all conditions.

Figure 3

(Color online) (a) Dispersion as a function of the external force for W-W homodimeric kinesins (solid line), for homodimeric M-M kinesins (dot-dashed line), and for W-M heterodimeric kinesins (dashed line) at $\left[\text{ATP}\right]=1\text{m}M$. (b) Dispersions of W-W homodimeric kinesins (solid line), homodimeric M-M kinesins (dot-dashed line), and W-M heterodimeric kinesins (dashed line) as a function of [ATP] at the constant external force $F=0.5\text{pN}$.