Microtubules are one kind of cytoskeleton that is ubiquitous in eukaryotic cells and is essential for various biological processes, such as intracellular transport, maintenance of cell morphology and cell division. Mi...Microtubules are one kind of cytoskeleton that is ubiquitous in eukaryotic cells and is essential for various biological processes, such as intracellular transport, maintenance of cell morphology and cell division. Microtubules are dynamic structures and the basic unit of microtubules is the heterodimer composed of α-tubulin and β-tubulin. The biological function of microtubules is based on their dynamic polymerization and depolymerization. However, the nucleotide-dependent depolymerization mechanism of microtubules is still unclear. The dynamic instability of microtubules is determined by the interactions between tubulins. In this work, the interactions between tubulins in the microtubule lattice(GDP at the interdimer interface) and in the special GTP-cap structure(GTP at the interdimer interface) are systematically investigated using all-atom molecular dynamics simulation method. The analysis of the tubulin–tubulin and nucleotide–tubulin interactions and binding free energy at different interfaces of microtubule shows that the hydrolysis of GTP can affect the longitudinal interaction between α-tubulin and β-tubulin at the interdimer interface and the lateral interaction between β-tubulins. In particular, the displacement of M loop of β-tubulin induced by GTP hydrolysis weakens the lateral interaction betweenβ-tubulins. Based on these results, a nucleotide-dependent depolymerization mechanism of microtubule induced by GTP hydrolysis is proposed.展开更多
基金Project supported by the Natural Science Foundation of Hebei Province of China (Grant No. A2023202010)。
文摘Microtubules are one kind of cytoskeleton that is ubiquitous in eukaryotic cells and is essential for various biological processes, such as intracellular transport, maintenance of cell morphology and cell division. Microtubules are dynamic structures and the basic unit of microtubules is the heterodimer composed of α-tubulin and β-tubulin. The biological function of microtubules is based on their dynamic polymerization and depolymerization. However, the nucleotide-dependent depolymerization mechanism of microtubules is still unclear. The dynamic instability of microtubules is determined by the interactions between tubulins. In this work, the interactions between tubulins in the microtubule lattice(GDP at the interdimer interface) and in the special GTP-cap structure(GTP at the interdimer interface) are systematically investigated using all-atom molecular dynamics simulation method. The analysis of the tubulin–tubulin and nucleotide–tubulin interactions and binding free energy at different interfaces of microtubule shows that the hydrolysis of GTP can affect the longitudinal interaction between α-tubulin and β-tubulin at the interdimer interface and the lateral interaction between β-tubulins. In particular, the displacement of M loop of β-tubulin induced by GTP hydrolysis weakens the lateral interaction betweenβ-tubulins. Based on these results, a nucleotide-dependent depolymerization mechanism of microtubule induced by GTP hydrolysis is proposed.
