| Autor: |
Guo W, Gao Y, Du D, Sanchez JE, Visootsat A, Li Y, Qiu W, Li L |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 Jun 02. Date of Electronic Publication: 2024 Jun 02. |
| DOI: |
10.1101/2024.05.31.596855 |
| Abstrakt: |
BimC family proteins are bipolar motor proteins belonging to the kinesin superfamily which promote mitosis by crosslinking and sliding apart antiparallel microtubules. Understanding the binding mechanism between the kinesin and the microtubule is crucial for researchers to make advances in the treatment of cancer and other malignancies. Experimental research has shown that the ion concentration affects the function of BimC significantly. But the insights of the ion-dependent function of BimC remain unclear. By combining molecular dynamics (MD) simulations with a series of computational approaches, we studied the electrostatic interactions at the binding interfaces of BimC and the microtubule under different KCl concentrations. We found the electrostatic interaction between BimC and microtubule is stronger at 0 mM KCl compared to 150 mM KCl, which is consistent with experimental conclusions. Furthermore, important salt bridges and residues at the binding interfaces of the complex were identified, which illustrates the details of the BimC-microtubule interactions. Molecular dynamics analyses of salt bridges identified that the important residues on the binding interface of BimC are positively charged, while those residues on the binding interface of the tubulin heterodimer are negatively charged. The finding in this work reveals some important mechanisms of kinesin-microtubule binding, which helps the future drug design for cancer therapy. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
