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Exploring the dynamics of flagellar dynein within the axoneme with Fluctuating Finite Element Analysis

Published online by Cambridge University Press:  10 August 2020

Robin A. Richardson Open the ORCID record for Robin A. Richardson [Opens in a new window] ,
Benjamin S. Hanson Open the ORCID record for Benjamin S. Hanson [Opens in a new window] ,
Daniel J. Read Open the ORCID record for Daniel J. Read [Opens in a new window] ,
Oliver G. Harlen Open the ORCID record for Oliver G. Harlen [Opens in a new window]  and
Sarah A. Harris Open the ORCID record for Sarah A. Harris [Opens in a new window]
Robin A. Richardson
Affiliation:
Department of Chemistry, University College London, London, UK
Benjamin S. Hanson
Affiliation:
School of Physics and Astronomy, University of Leeds, Leeds, UK
Daniel J. Read
Affiliation:
School of Mathematics, University of Leeds, Leeds, UK
Oliver G. Harlen
Affiliation:
School of Mathematics, University of Leeds, Leeds, UK
Sarah A. Harris*
Affiliation:
School of Physics and Astronomy, University of Leeds, Leeds, UK Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, UK
*
Author for correspondence: Sarah A Harris, E-mail: s.a.harris@leeds.ac.uk
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Abstract

Flagellar dyneins are the molecular motors responsible for producing the propagating bending motions of cilia and flagella. They are located within a densely packed and highly organised super-macromolecular cytoskeletal structure known as the axoneme. Using the mesoscale simulation technique Fluctuating Finite Element Analysis (FFEA), which represents proteins as viscoelastic continuum objects subject to explicit thermal noise, we have quantified the constraints on the range of molecular conformations that can be explored by dynein-c within the crowded architecture of the axoneme. We subsequently assess the influence of crowding on the 3D exploration of microtubule-binding sites, and specifically on the axial step length. Our calculations combine experimental information on the shape, flexibility and environment of dynein-c from three distinct sources; negative stain electron microscopy, cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET). Our FFEA simulations show that the super-macromolecular organisation of multiple protein complexes into higher-order structures can have a significant influence on the effective flexibility of the individual molecular components, and may, therefore, play an important role in the physical mechanisms underlying their biological function.

Keywords

CrowdingdyneinFFEAmesoscaleparameterisationsimulation
Type
Short Review
Information
Quarterly Reviews of Biophysics , Volume 53 , 2020 , e9
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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Footnotes

*

These authors contributed equally to this work.

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