中国物理B ›› 2026, Vol. 35 ›› Issue (2): 28701-028701.doi: 10.1088/1674-1056/adf4a8

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Mechanism of loop-2 in facilitating microtubule depolymerase activity of kinesin-8 motors

Xiao-Xuan Shi(史晓璇)1,2, Yao Wang(王瑶)2, Jie Wang(王杰)2, Yu-Ru Liu(刘玉如)2, and Ping Xie(谢平)2,†   

  1. 1 School of Pharmaceutical Engineering, Chongqing Chemical Industry Vocational College, Chongqing 401220, China;
    2 Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China
  • 收稿日期:2025-05-29 修回日期:2025-07-17 接受日期:2025-07-28 发布日期:2026-01-31
  • 通讯作者: Ping Xie E-mail:pxie@aphy.iphy.ac.cn
  • 基金资助:
    Project supported by the Science and Technology Research Program of Chongqing Municipal Education Commission (Grant No. KJQN202504529) and the General Program of Chongqing Natural Science Foundation (Grant No. CSTB2025NSCQ-GPX0833).

Mechanism of loop-2 in facilitating microtubule depolymerase activity of kinesin-8 motors

Xiao-Xuan Shi(史晓璇)1,2, Yao Wang(王瑶)2, Jie Wang(王杰)2, Yu-Ru Liu(刘玉如)2, and Ping Xie(谢平)2,†   

  1. 1 School of Pharmaceutical Engineering, Chongqing Chemical Industry Vocational College, Chongqing 401220, China;
    2 Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China
  • Received:2025-05-29 Revised:2025-07-17 Accepted:2025-07-28 Published:2026-01-31
  • Contact: Ping Xie E-mail:pxie@aphy.iphy.ac.cn
  • Supported by:
    Project supported by the Science and Technology Research Program of Chongqing Municipal Education Commission (Grant No. KJQN202504529) and the General Program of Chongqing Natural Science Foundation (Grant No. CSTB2025NSCQ-GPX0833).

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摘要： Kinesin-8 motors can move with a high processivity on microtubule lattices toward the plus end. After reaching the plus end, the kinesin-8 motors can pause for a long time and promote the microtubule depolymerization. Here, using atomistic molecular dynamics simulations we studied the structural changes of the kinesin-8 head in different nucleotide states bound to the straight and curved tubulins and the corresponding interactions between them. We found that the kinesin-8 head in ATP and/or ADP-Pi state has the similar strong affinity while in ADP state has the similar weak affinity to both the straight and curved tubulins, which is strongly implicated in the mechanism of the long but very different residence times of the kinesin-8 motor on the microtubule lattice and at the end. Moreover, we found that loop-2 of the kinesin-8 head bound strongly to the curved tubulin in the stable state has a large interference with its neck linker pulled in the minus-ended orientation. This is contrary to the case of the head bound strongly to the straight tubulin, where loop-2 has little interference with its neck linker pulled in the minus-ended orientation. The large interference can induce a larger internal force between the two heads and thus can induce the two curved tubulins bound strongly by the two heads to be more curved relative to each other. This is strongly implicated in the mechanism of the depolymerase activity of the kinesin-8 motors and explains the origin of loop-2 playing a facilitating role in the depolymerase activity.

关键词: microtubule depolymerization, kinesin, binding energy, straight tubulin, curved tubulins, molecular dynamics simulation

Abstract: Kinesin-8 motors can move with a high processivity on microtubule lattices toward the plus end. After reaching the plus end, the kinesin-8 motors can pause for a long time and promote the microtubule depolymerization. Here, using atomistic molecular dynamics simulations we studied the structural changes of the kinesin-8 head in different nucleotide states bound to the straight and curved tubulins and the corresponding interactions between them. We found that the kinesin-8 head in ATP and/or ADP-Pi state has the similar strong affinity while in ADP state has the similar weak affinity to both the straight and curved tubulins, which is strongly implicated in the mechanism of the long but very different residence times of the kinesin-8 motor on the microtubule lattice and at the end. Moreover, we found that loop-2 of the kinesin-8 head bound strongly to the curved tubulin in the stable state has a large interference with its neck linker pulled in the minus-ended orientation. This is contrary to the case of the head bound strongly to the straight tubulin, where loop-2 has little interference with its neck linker pulled in the minus-ended orientation. The large interference can induce a larger internal force between the two heads and thus can induce the two curved tubulins bound strongly by the two heads to be more curved relative to each other. This is strongly implicated in the mechanism of the depolymerase activity of the kinesin-8 motors and explains the origin of loop-2 playing a facilitating role in the depolymerase activity.

Key words: microtubule depolymerization, kinesin, binding energy, straight tubulin, curved tubulins, molecular dynamics simulation

中图分类号:  (Molecular dynamics simulation)

  • 87.10.Tf
87.15.A- (Theory, modeling, and computer simulation) 87.15.hg (Dynamics of intermolecular interactions)