Depolymerization mechanism of microtubule revealed by nucleotide-dependent changes of longitudinal and lateral interactions

doi:10.1088/1674-1056/adc369

中国物理B ›› 2025, Vol. 34 ›› Issue (6): 68702-068702.doi: 10.1088/1674-1056/adc369

Depolymerization mechanism of microtubule revealed by nucleotide-dependent changes of longitudinal and lateral interactions

Bingbing Zhang(张冰冰)^1,2, Ziling Huo(霍子玲)¹, Jiaxi Li(李佳希)¹, Jingyu Qin(覃静宇)^3,†, and Yizhao Geng(耿轶钊)^2,4,‡

1 School of Health Sciences & Biomedical Engineering, Hebei University of Technology, Tianjin 300401, China;
2 School of Science, Hebei University of Technology, Tianjin 300401, China;
3 College of Electrical and Information Engineering, Quzhou University, Quzhou 324000, China;
4 Key Laboratory of Molecular Biophysics of Hebei Province, Hebei University of Technology, Tianjin 300401, China

收稿日期:2025-02-05 修回日期:2025-03-09 接受日期:2025-03-21 出版日期:2025-05-16 发布日期:2025-05-27
通讯作者: Jingyu Qin, Yizhao Geng E-mail:jingyuqin@qzc.edu.cn;gengyz@hebut.edu.cn
基金资助:
Project supported by the Natural Science Foundation of Hebei Province of China (Grant No. A2023202010).

Depolymerization mechanism of microtubule revealed by nucleotide-dependent changes of longitudinal and lateral interactions

Bingbing Zhang(张冰冰)^1,2, Ziling Huo(霍子玲)¹, Jiaxi Li(李佳希)¹, Jingyu Qin(覃静宇)^3,†, and Yizhao Geng(耿轶钊)^2,4,‡

1 School of Health Sciences & Biomedical Engineering, Hebei University of Technology, Tianjin 300401, China;
2 School of Science, Hebei University of Technology, Tianjin 300401, China;
3 College of Electrical and Information Engineering, Quzhou University, Quzhou 324000, China;
4 Key Laboratory of Molecular Biophysics of Hebei Province, Hebei University of Technology, Tianjin 300401, China

Received:2025-02-05 Revised:2025-03-09 Accepted:2025-03-21 Online:2025-05-16 Published:2025-05-27
Contact: Jingyu Qin, Yizhao Geng E-mail:jingyuqin@qzc.edu.cn;gengyz@hebut.edu.cn
Supported by:
Project supported by the Natural Science Foundation of Hebei Province of China (Grant No. A2023202010).

1. 2025-068702-SI.pdf(1478KB)

摘要/Abstract

摘要： 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 $\alpha$-tubulin and $\beta $-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 $\alpha$-tubulin and $\beta $-tubulin at the interdimer interface and the lateral interaction between $\beta $-tubulins. In particular, the displacement of M loop of $\beta $-tubulin induced by GTP hydrolysis weakens the lateral interaction between $\beta $-tubulins. Based on these results, a nucleotide-dependent depolymerization mechanism of microtubule induced by GTP hydrolysis is proposed.

关键词: microtubule, tubulin, dynamic instability, molecular dynamics simulation

Abstract: 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 $\alpha$-tubulin and $\beta $-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 $\alpha$-tubulin and $\beta $-tubulin at the interdimer interface and the lateral interaction between $\beta $-tubulins. In particular, the displacement of M loop of $\beta $-tubulin induced by GTP hydrolysis weakens the lateral interaction between $\beta $-tubulins. Based on these results, a nucleotide-dependent depolymerization mechanism of microtubule induced by GTP hydrolysis is proposed.

Key words: microtubule, tubulin, dynamic instability, molecular dynamics simulation

中图分类号: (Filaments, microtubules, their networks, and supramolecular assemblies)

87.16.Ka

87.10.Tf (Molecular dynamics simulation) 87.15.-v (Biomolecules: structure and physical properties) 87.15.km (Protein-protein interactions)

Bingbing Zhang(张冰冰), Ziling Huo(霍子玲), Jiaxi Li(李佳希), Jingyu Qin(覃静宇), and Yizhao Geng(耿轶钊). Depolymerization mechanism of microtubule revealed by nucleotide-dependent changes of longitudinal and lateral interactions[J]. 中国物理B, 2025, 34(6): 68702-068702.

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Depolymerization mechanism of microtubule revealed by nucleotide-dependent changes of longitudinal and lateral interactions

Depolymerization mechanism of microtubule revealed by nucleotide-dependent changes of longitudinal and lateral interactions

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