The impact of a catalytic site mutation on the shape and mechanics of tubulin protofilaments

Alpha-beta heterodimers of tubulin proteins serve as the building blocks of microtubules, which are key biopolymers forming one of the principal systems of the cellular cytoskeleton. A detailed study of these building blocks, as well as their alterations caused by point mutations, contributes to a deeper understanding of physiological and pathological processes related to the cytoskeleton. This study presents an analysis of the impact of the E254N point mutation in the catalytic site of $\alpha$-tubulin on the bending conformations of human recombinant tubulin tetramers using molecular dynamics methods. The models were constructed based on high-resolution cryo-electron microscopy data, allowing the reconstruction of three-dimensional structures of both wild-type and mutant tetramers. The simulations revealed that the primary difference between wild-type and mutant tubulin lies in the equilibrium bending direction of the protofilaments, while the bending amplitude, twisting, and associated stiffness remain largely unchanged. We propose that the observed differences in bending directions may be related to variations in protofilament tilts within microtubules, which aligns with previously published cryo-electron microscopy data. These findings provide valuable insights into the principles underlying the formation of the polymeric structure of microtubules based on the properties of their individual building blocks.