Gating of MscL studied by steered molecular dynamics
Gating of MscL studied by steered molecular dynamics
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DOI：
10.1016/s0006-3495(03)74637-2
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发表时间：
2003-10-01
影响因子：
3.4
通讯作者：
Schulten, K
中科院分区：
文献类型：
--
作者：
Gullingsrud, J;Schulten, K
大电导机械敏感通道（MscL）的操纵分子动力学模拟被用来研究膜张力产生的力如何诱导通道的门控。在膜-水界面附近的残基上施加35-70 pN的外力，建立了封闭形式的大肠杆菌同源性模型。这些力的大小和位置与通过脂质双分子层模拟计算得到的侧压力分布相对应。在10-ns时间尺度上获得了完全展开状态，揭示了膜力转化为通道打开的机制。扩展状态与提出的MscL门控制模型很好地一致，因为它需要虹膜状的孔扩张伴随着跨膜螺旋的倾斜。当主要在MscL细胞质侧施加力时，通道最容易打开。在门控进展到不同程度的模拟比较中，确定了对通道打开构成位阻的残基。
Steered molecular dynamics simulations of the mechanosensitive channel of large conductance, MscL, were used to investigate how forces arising from membrane tension induce gating of the channel. A homology model of the closed form of MscL from Escherichia coli was subjected to external forces of 35-70 pN applied to residues near the membrane-water interface. The magnitude and location of these forces corresponded to those determined from the lateral pressure profile computed from a lipid bilayer simulation. A fully expanded state was obtained on the 10-ns timescale that revealed the mechanism for transducing membrane forces into channel opening. The expanded state agrees well with proposed models of MscL gating, in that it entails an irislike expansion of the pore accompanied by tilting of the transmembrane helices. The channel was most easily opened when force was applied predominantly on the cytoplasmic side of MscL. Comparison of simulations in which gating progressed to varying degrees identified residues that pose steric hindrance to channel opening.