Computational Study on E-Hooks of Tubulins in the Binding Process with Kinesin

Lin Li,Yixin Xie

doi:10.3390/ijms23042035

Abstract

Cargo transport within cells is essential to healthy cells, which requires microtubules-based motors, including kinesin. The C-terminal tails (E-hooks) of alpha and beta tubulins of microtubules have been proven to play important roles in interactions between the kinesins and tubulins. Here, we implemented multi-scale computational methods in E-hook-related analyses, including flexibility investigations of E-hooks, binding force calculations at binding interfaces between kinesin and tubulins, electrostatic potential calculations on the surface of kinesin and tubulins. Our results show that E-hooks have several functions during the binding process: E-hooks utilize their own high flexibilities to increase the chances of reaching a kinesin; E-hooks help tubulins to be more attractive to kinesin. Besides, we also observed the differences between alpha and beta tubulins: beta tubulin shows a higher flexibility than alpha tubulin; beta tubulin generates stronger attractive forces (about twice the strengths) to kinesin at different distances, no matter with E-hooks in the structure or not. Those facts may indicate that compared to alpha tubulin, beta tubulin contributes more to attracting and catching a kinesin to microtubule. Overall, this work sheds the light on microtubule studies, which will also benefit the treatments of neurodegenerative diseases, cancer treatments, and preventions in the future.

Highlights

Molecular motors are essential for living organisms as they take charge of converting energy into motion or mechanical work, including cargo transport of organelles, secretory vesicles and protein complexes in an extremely efficient way, which are superior to current human-made motors [1,2]
Our results show that E-hooks have several functions during the binding process: E-hooks utilize their own high flexibility in a solvent to increase the chances of finding a kinesin, based on the E-hook flexibility analyses; E-hooks help tubulins to be more attractive to kinesin, based on the electrostatic calculations
We observed the differences between alpha and beta tubulins: beta tubulin shows a higher flexibility than alpha tubulin, based on the E-hooks flexibility analyses; beta tubulin generates higher attractive forces to kinesin at different distances, no matter with E-hooks in the structure or not, based on the force calculations

Summary

Introduction

Molecular motors are essential for living organisms as they take charge of converting energy into motion or mechanical work, including cargo transport of organelles, secretory vesicles and protein complexes in an extremely efficient way, which are superior to current human-made motors [1,2]. Normal kinee.gsin is crucial to a healthy cell, as certain types of mutations on kinesin proteins lead to nervous system disorders such as peripheral neuropathy [8]. Kinesins perform their functions by moving along on microtubules. Microtubules are cytoskeletal structures that are formed by the self-assembly of alpha-beta tubulin heterodimers (~450 amino acids each) [8,9]. They are 17 nm in interior diameter and 25 nm in the outer. The abnormalities of microtubules are associated with neurodegenerative diseases [12]

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Results

Conclusion