A multi-state dynamic process confers mechano-adaptation to a biological nanomachine.

A multi-state dynamic process confers mechano-adaptation to a biological nanomachine.
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DOI:
10.1038/s41467-022-33075-5
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发表时间:
2022-09-10
影响因子:
16.6
通讯作者:
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中科院分区:
综合性期刊1区
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适应是生命系统的一个决定性特征。细菌鞭毛马达通过添加或移除扭矩产生(定子)单元来适应外部机械负载的变化。但这种机械适应背后的分子机制仍不清楚。在这里,我们结合联合收割机单电机eletrorotation的实验和理论建模表明,鞭毛电机的机械适应是由多个mechanosensitive内部状态。驻留时间统计实验表明,存在至少两个绑定状态,分别具有高和低的解绑定率。四态模型的首次穿越时间分析定量地解释了实验数据,并确定了所有四个状态之间的跃迁速率。由绑定定子单元产生的扭矩通过调制绑定状态之间的过渡(可能经由捕获键合机制)来控制它们的有效解绑定速率。类似的由多个内部状态实现的力介导的反馈可能适用于其他大分子复合物的适应。结合实验与建模,Wadhwa等人提出了细菌鞭毛马达中的机械适应模型,发现多个内部状态之间的负载依赖性转换控制亚基的结合和解结合。
Adaptation is a defining feature of living systems. The bacterial flagellar motor adapts to changes in the external mechanical load by adding or removing torque-generating (stator) units. But the molecular mechanism behind this mechano-adaptation remains unclear. Here, we combine single motor eletrorotation experiments and theoretical modeling to show that mechano-adaptation of the flagellar motor is enabled by multiple mechanosensitive internal states. Dwell time statistics from experiments suggest the existence of at least two bound states with a high and a low unbinding rate, respectively. A first-passage-time analysis of a four-state model quantitatively explains the experimental data and determines the transition rates among all four states. The torque generated by bound stator units controls their effective unbinding rate by modulating the transition between the bound states, possibly via a catch bond mechanism. Similar force-mediated feedback enabled by multiple internal states may apply to adaptation in other macromolecular complexes. Combining experiments with modeling, Wadhwa et al. propose a model for mechano-adaptation in the bacterial flagellar motor, finding that load-dependent transitions between multiple internal states govern the binding and unbinding of subunits.
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