Richardson, RA orcid.org/0000-0002-9984-2720, Hanson, BS orcid.org/0000-0002-6079-4506, Read, DJ orcid.org/0000-0003-1194-9273 et al. (2 more authors) (2020) Exploring the dynamics of flagellar dynein within the axoneme with Fluctuating Finite Element Analysis. Quarterly Reviews of Biophysics, 53. e9. ISSN 0033-5835
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s), 2020. Published by Cambridge University Press. This is an author produced version of an article published in Quarterly Reviews of Biophysics. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Crowding; dynein; FFEA; mesoscale; parameterisation; simulation |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Mathematics (Leeds) > Applied Mathematics (Leeds) The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Physics and Astronomy (Leeds) > Molecular & Nanoscale Physics The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Physics and Astronomy (Leeds) > Theoretical Physics (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 17 Aug 2020 12:14 |
Last Modified: | 02 Jan 2025 11:40 |
Status: | Published |
Publisher: | Cambridge University Press |
Identification Number: | 10.1017/s0033583520000062 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:164279 |