ИСТИНА

Tubulin microtubules are essential cytoskeletal filaments, with diverse and critical functions at all stages of the cell cycle. Tubulin dimers, which serve as main building blocks for microtubules, can self-assemble and disassemble, depending on the phosphorylation state of associated nucleotide. Tubulins bound to guanosine triphosphate (GTP) make stable microtubule lattice, but when the GTP molecules lose their γ-phosphates, microtubules become prone to depolymerization. The relationship between tubulin conformation and GTP hydrolysis is still poorly understood. Recent progress in cryo-electron microscopy and related data analysis methods have brought new critical insights into the nucleotide-dependent structure of microtubule lattice (Alushin et al., Cell, 2014; Manka et al., Nat. Struct. Mol. Biol., 2018; Zhang et al., PNAS, 2018). However, supplementary methods are needed to bridge static cryo-electron microscopy-based structures with microtubule dynamic instability. Here we use all-atom molecular dynamics (MD) simulations to examine relaxed conformations and mechanical properties of tubulin dimers, extracted from cryo- electron microscopy-based tubulin structures of different generations. This analysis enables us to draw conclusions about the mechanism for microtubule dynamic instability.