Abstract:
The tubulin cytoskeleton, consisting of a network of microtubules, is a key intracellular system that supports the execution of numerous vital cellular functions. Its operation is regulated by post-translational modifications, which are introduced and edited by enzymes, recognized by regulatory proteins, or directly influence the properties of tubulins. One such modification is the polyglutamylation of the C-terminal regions of tubulin. In this study, we investigated the effect of adding additional glutamate residues on the dynamics of the C-terminal regions of $\alpha$-tubulin and their interactions with the globular domains of tubulin using all-atom molecular dynamics simulations. The analysis of simulation data totaling over three microseconds for both modified and unmodified tubulin revealed that polyglutamylation decreases the average distance between the base and the tip of the unstructured C-terminal region, increasing the likelihood of its contact with the globular domain of the protein, including the polymerization interface. These findings suggest that polyglutamylation of the C-terminal regions of $\alpha$-tubulin may act as a factor influencing the kinetics of microtubule assembly.
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