Exploring the dynamics of flagellar dynein within the axoneme with Fluctuating Finite Element Analysis. (2020)

• Record Type: Journal Article
• Authors: Richardson, Robin A.; Hanson, Benjamin S.; Read, Daniel J.; Harlen, Oliver G.; Harris, Sarah A.
• Is Part Of: Quarterly reviews of biophysics. Volume 53(2020)
• Publication Date: 2020
• Subjects: Crowding, -- dynein, -- FFEA, -- mesoscale, -- parameterisation, -- simulation; Biophysics -- Periodicals; 571.405
• DOI: 10.1017/S0033583520000062
• Languages: English
• ISSNs: 0033-5835

Abstract

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.