Effect of Kinesin-5 Tail Domain on Motor Dynamics for Antiparallel Microtubule Sliding

Abstract

Kinesin-5 motor consists of two pairs of heads and tail domains, which are situated at the opposite ends of a common stalk. The two pairs of heads can bind to two antiparallel microtubules (MTs) and move on the two MTs independently towards the plus ends, sliding apart the two MTs, which is responsible for chromosome segregation during mitosis. Prior experimental data showed that the tails of kinesin-5 Eg5 can modulate the dynamics of single motors and are critical for multiple motors to generate high steady forces to slide apart two antiparallel MTs. To understand the molecular mechanism of the tails modulating the ability of Eg5 motors, based on our proposed model the dynamics of the single Eg5 with the tails and that without the tails moving on single MTs is studied analytically and compared. Furthermore, the dynamics of antiparallel MT sliding by multiple Eg5 motors with the tails and that without the tails is studied numerically and compared. Both the analytical results for single motors and the numerical results for multiple motors are consistent with the available experimental data.

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“…To calculate the force generated by Eg5 ensembles, besides the forward stepping rate k F (m) , the backward stepping rate k B (m) and the dissociation rate k off (m) for the Eg5 motor, the values of two other parameters k 0 (m) and μ m are required, where k 0 (m) is the second-order rate of the motor in solution binding to one MT and μ m is the binding rate of one pair of the heads to one MT when another pair of the heads at the opposite end of the stalk are attached to another MT in the overlap zone (see Section ). The values of parameters k F (m) , k B (m) , and k off (m) can be calculated with the rate constants of the ATPase activity and other parameters of the single motor during its processive movement on the single MT, which were determined before (see Table S2). Here, we adjust the values of k 0 (m) and μ m to make the calculated results consistent with the prior experimental data .…”

“…Here, we use the model for the processive stepping of the full-length kinesin-5 Eg5 motor as proposed before, which was modified from the general model for the N-terminal kinesin dimers. − In the model for the full-length Eg5 motor, the effect of the tail domain on the motor dynamics was considered (see Section S1 in the Supporting Information). ,− Upon binding to a MT filament, each pair of MT-bound heads of the Eg5 motor can move along the filament with the period of the binding sites being d = 8.2 nm . The pair of heads of the Eg5 motor can take a forward (plus-ended-directed) step with rate k F (m) and a backward (minus-ended-directed) step with rate k B (m) (see Section S1 in the Supporting Information).…”

“…When only one pair of heads of Eg5 is attached to one MT, another pair of heads at the opposite end of the stalk can bind to the antiparallel MT with rate μ m . The values of k F (m) , k B (m) , and k off (m) have been determined before (see Section S1). The values of k 0 (m) and μ m can be obtained by comparing the numerical results with the prior experimental data, which will be shown in the Results section.…”

“…To (m) , k B (m) , and k off (m) can be calculated with the rate constants of the ATPase activity and other parameters of the single motor during its processive movement on the single MT, which were determined before 41 (see Table S2). Here, we adjust the values of k 0 (m) and μ m to make the calculated results consistent with the prior experimental data.…”

“…Motors. Here, we use the model for the processive stepping of the full-length kinesin-5 Eg5 motor as proposed before, 41 which was modified from the general model for the N-terminal kinesin dimers. 42−44 In the model for the full-length Eg5 motor, the effect of the tail domain on the motor dynamics was considered (see Section S1 in the Supporting Information).…”