Atomistic molecular dynamics simulations of tubulin heterodimers explain the motion of a microtubule

Alexandr Nasedkin,Inna Ermilova,Jan Swenson

doi:10.1007/s00249-021-01553-1

Alexandr Nasedkin, Inna Ermilova + Show 1 more

Open Access

https://doi.org/10.1007/s00249-021-01553-1

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Abstract

Microtubules are essential parts of the cytoskeleton that are built by polymerization of tubulin heterodimers into a hollow tube. Regardless that their structures and functions have been comprehensively investigated in a modern soft matter, it is unclear how properties of tubulin heterodimer influence and promote the self-assembly. A detailed knowledge of such structural mechanisms would be helpful in drug design against neurodegenerative diseases, cancer, diabetes etc. In this work atomistic molecular dynamics simulations were used to investigate the fundamental dynamics of tubulin heterodimers in a sheet and a short microtubule utilizing well-equilibrated structures. The breathing motions of the tubulin heterodimers during assembly show that the movement at the lateral interface between heterodimers (wobbling) dominates in the lattice. The simulations of the protofilament curvature agrees well with recently published experimental data, showing curved protofilaments at polymerization of the microtubule plus end. The tubulin heterodimers exposed at the microtubule minus end were less curved and displayed altered interactions at the site of sheet closure around the outmost heterodimers, which may slow heterodimer binding and polymerization, providing a potential explanation for the limited dynamics observed at the minus end.

Highlights

Biological cells and their components have always been of high interest in the soft matter community (Lam et al 2014; Edozie et al 2019; Pan et al 2014; Gallová et al 2004; Murtola et al 2009)
A similar behavior was observed in other computational works for protofilaments and entire microtubules (Wells and Aksimentiev 2010; Deriu et al 2010)
Growth and dynamics of microtubules have been a major focus of research efforts for decades

Summary

Introduction

Biological cells and their components have always been of high interest in the soft matter community (Lam et al 2014; Edozie et al 2019; Pan et al 2014; Gallová et al 2004; Murtola et al 2009). Microtubules consist of tubulin heterodimers and they are an essential part of the cytoskeleton (Goddard et al 1994; Kapitein and Hoogenraad 2015; Fojo 2009). They are hollow cylinders with walls that are formed by laterally bound parallel filaments of tubulin, called protofilaments (PF) (Jibu et al 1994). Microtubules and their dynamics play a big role in neurodegenerative diseases (Matamoros and Baas 2016). In neurodegenerative diseases the mass of the microtubule is reduced, its electrostatic and a microtubulemediated transport get disintegrated

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