Elucidating the interactions between Kinesin-5/BimC and the microtubule: insights from TIRF microscopy and molecular dynamics simulations

阐明驱动蛋白-5/BimC与微管之间的相互作用:来自TIRF显微镜和分子动力学模拟的见解

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Abstract

Kinesin-5 s are bipolar motor proteins that contribute to cell division by crosslinking and sliding apart antiparallel microtubules inside the mitotic spindle. However, the mechanism underlying the interactions between kinesin-5 and the microtubule remains poorly understood. In this study, we investigated the binding of BimC, a kinesin-5 motor from Aspergillus nidulans, to the microtubule using a combination of total internal reflection fluorescence (TIRF) microscopy and molecular dynamics (MD) simulations. TIRF microscopy experiments revealed that increasing the concentration of KCl in the motility buffer from 0 mM to 150 mM completely abolishes the ability of BimC to bind to the microtubule. Consistent with this experimental finding, MD simulations demonstrated a significant reduction in the strength of electrostatic interactions between BimC and microtubules at 150 mM KCl compared to 0 mM KCl. Furthermore, we identified several salt bridges at the BimC-microtubule interface, with positively charged residues on BimC interacting with negatively charged residues on the tubulin heterodimer. These results provide mechanistic insights into the role of electrostatic interactions in kinesin-5-microtubule binding, advancing our understanding of the molecular underpinnings of kinesin-5 motility.

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