Tension mediated mechanical activation and pocket delipidation lead to an analogous MscL state

Tension mediated mechanical activation and pocket delipidation lead to an analogous MscL state
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张力介导的机械激活和口袋脱脂导致类似的 MscL 状态

DOI:
10.1101/2021.04.01.438050
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发表时间:
2021
期刊:
--
影响因子:
--
通讯作者:
Wang B
Wang B
中科院分区:
--
文献类型:
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作者:
Wang B

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MscL通道响应膜张力变化而进行门控,以允许分子通过其孔隙进行交换。从跨膜口袋中除去脂质导致MscL应答。然而,尚不清楚张力介导的状态与在不存在张力的情况下通过囊袋脱脂获得的状态之间是否存在相关性。MscL状态之间的转换可能遵循类似的途径来覆盖可用的构象空间,但可能不一定对相同的离散中间体进行采样。在这里,我们结合脉冲EPR和HDX-MS测量MscL,再加上膜张力下的分子动力学,研究与独特的衍生状态相关的变化。无论是张力或口袋脱脂,我们发现,MscL样品一个类似的扩展状态,这是脱脂途径的最后一步,但只是一个中间停止张力介导的path. Our研究结果提示在机械敏感通道的调节协同模式。
The MscL channel gates in response to membrane tension changes to allow the exchange of molecules through its pore. Lipid removal from transmembrane pockets leads to a MscL response. However, it is unknown whether there is correlation between the tension mediated state and the state derived by pocket delipidation in the absence of tension. Transitions between MscL states may follow a similar pathway to cover the available conformational space but may not necessarily sample the same discrete intermediates. Here, we combined pulsed-EPR and HDX-MS measurements on MscL, coupled with molecular dynamics under membrane tension, to investigate the changes associated with the distinctively derived states. Whether it is tension or pocket delipidation, we find that MscL samples a similar expanded state, which is the final step of the delipidation pathway but only an intermediate stop of the tension mediated path. Our findings hint at synergistic modes of regulation in mechanosensitive channels.
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