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

Yuying Liu,Pengye Wang,Ping Xie,Yao Wang

doi:10.3390/ijms22157857

Yuying Liu, Pengye Wang + Show 2 more

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https://doi.org/10.3390/ijms22157857

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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.

Highlights

Kinesin-5 molecular motors constitute a subfamily of the large kinesin superfamily that can perform various functions in cells such as cargo transport, chromosome segregation, spindle assembly, cytoskeletal organization, etc., via interacting with microtubules (MTs) [1,2,3]
By making use of the chemical energy released from ATP hydrolysis the two pairs of heads can move on the two antiparallel MTs independently, sliding apart the two MTs, responsible for chromosome segregation during mitosis [6,7,8,9]
We denote by kD the rate of ADP release from the head bound to MT, which for simplicity is treated here to be independent of neck linker (NL) direction and force on NL

Summary

Introduction

Kinesin-5 molecular motors constitute a subfamily of the large kinesin superfamily that can perform various functions in cells such as cargo transport, chromosome segregation, spindle assembly, cytoskeletal organization, etc., via interacting with microtubules (MTs) [1,2,3]. A kinesin-5 motor is a homotetramer, consisting of two pairs of N-terminal motor domains (or heads) and two pairs of C-terminal tail domains, which are situated at the opposite ends of a common 60-nm-long rod-like stalk [4,5] (see Figure S1 in Supplementary Materials). Each head is connected to the stalk via its flexible neck linker (NL) of. Except for some fungal kinesin-5 motors such as S. cerevisiae Cin and

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