Unbinding of Kinesin from Microtubule in the Strongly Bound States Enhances under Assisting Forces

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Khataee, Hamidreza
Naseri, Solmaz
Zhong, Yongmin
Liew, Alan Wee-Chung
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2018
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Abstract

The ability to predict the cellular dynamics of intracellular transport has enormous potential to impact human health. A key transporter is kinesin‐1, an ATP‐driven molecular motor that shuttles cellular cargos along microtubules (MTs). The dynamics of kinesins depends critically on their unbinding rate from MT, which varies depending on the force direction applied on the motor, i.e. the force‐unbinding rate relation is asymmetric. However, it remains unclear how changing the force direction from resisting (applied against the motion direction) to assisting (applied in the motion direction) alters the kinesin's unbinding and stepping. Here, we propose a theoretical model for the influence of the force direction on the stepping dynamics of a single kinesin. The model shows that the asymmetry of the force‐unbinding rate relation is independent of ATP concentration. It also reveals that the synthesis of ATP from backward stepping under assisting forces is less likely than under resisting forces. It then finds that the unbinding of kinesin in the strongly MT‐bound kinetic states enhances under assisting forces.

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Molecular Informatics

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37

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4

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Medicinal and biomolecular chemistry

Theoretical and computational chemistry

Theoretical and computational chemistry not elsewhere classified

Biochemistry and cell biology

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