Microtubules are a critical component of the eukaryotic cell cytoskeleton, and the nucleotide state of the tubulin dimer is known to control aspects of microtubule growth, stability, and interactions. Much work has been done studying how the nucleotide state affects binding of microtubule-associated proteins as well as lattice conformation, colloquially dubbed “expanded” and “compacted.” However, because the C-terminal tails are disordered, structural studies have provided little insight into their dynamics and interactions. In order to address this gap, we have used all-atom molecular dynamics simulations of both GTP and GDP microtubules to determine the interactions of the C-terminal tails. We find that C-terminal tails exhibit strong electrostatic interactions with several different regions of the microtubule body. Since the interactions are dynamics and there are a multiplicity of bound conformations, these interactions would not be readily observable in structural studies. Interestingly, we see more frequent and long-lived interactions in the GDP state as compared to the GTP state. This suggests that the C-terminal tail is a direct readout of the nucleotide state of the microtubule that can be used by molecular motors and other interacting proteins.
DeLear et al. (Sun,) studied this question.