The Coordination and Regulation of Axonemal Dynein

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Molecular motor proteins drive the motility behind cellular dynamics. Recent advances in structural biology and single-molecule biophysics have led to a detailed understanding of many motor protein mechanisms. However, two understudied areas include the regulation and the coordination of motor proteins, particularly axonemal dyneins, which are the motors that drive the motility of eukaryotic cilia and flagella. Here we reconstitute motor motility in vitro using purified protein components to study the regulation of axonemal dynein by the biochemistry of the microtubules upon which they act. We find that axonemal dynein's motile properties are regulated differently depending on the source of tubulin in the experiments and the post translational modification of these microtubules. We also apply multi-scale computational methods to dynein microtubule binding domains and show how electrostatic interactions affect multiple aspects of dynein's motility. These effects include how interactions with the highly charged C-terminal tails, the location of many post-translational modifications of microtubules, could regulate motility. Finally, we show how these regulation mechanisms could lead to cooperation amongst teams of axonemal dynein motors and coordination of the eukaryotic ciliary beat.