Biophysical Mechanisms of Membrane-Thickness-Dependent MscL Gating: An All-Atom Molecular Dynamics Study.
Biophysical Mechanisms of Membrane-Thickness-Dependent MscL Gating: An All-Atom Molecular Dynamics Study.
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膜厚度依赖性 MscL 门控的生物物理机制：全原子分子动力学研究。
DOI：
10.1021/acs.langmuir.8b02074
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
M. Sokabe
中科院分区：
文献类型：
--
作者：
Hiroki Katsuta;Y. Sawada;M. Sokabe
细菌机械敏感通道，MscL，被膜张力激活，作为一个安全阀，防止细胞裂解对抗低渗挑战。已确定其激活阈值随膜厚度的增加而降低，但其作用机制尚不清楚。我们用全原子分子动力学（MD）模拟了MscL包埋在四种不同厚度的脂质双层中的初始打开过程：1,2-二脲酰- sn-甘油-3-磷脂胆碱（DLPC）、1,2-二myristoyl-甘油-3-磷酸胆碱（DMPC）、1,2-二棕榈酰- sn-甘油-3-磷脂胆碱（DPPC）和1,2-二硬脂酰- sn-甘油-3-磷脂胆碱（dsc）。在膜拉伸的作用下，通道打开只发生在较薄的膜（DLPC和DMPC）上，并且以厚度依赖的方式发生。我们发现MscL的开口受膜变薄的速率和程度的控制，通道开口与MscL的跨膜螺旋向膜平面倾斜密切相关。拉伸后，较薄膜（DLPC和DMPC）的酰基链序参数变小，而较厚膜（DPPC和dsc）的酰基链序参数变化不大。序参量的降低对膜变薄的贡献大于指间化。我们得出结论，膜厚度依赖性MscL开口主要是由MscL的结构变化引起的，以配合膜厚度的改变。
The bacterial mechanosensitive channel, MscL, is activated by membrane tension, acting as a safety valve to prevent cell lysis against hypotonic challenge. It has been established that its activation threshold decreases with membrane thickness, while the underlying mechanism remains to be solved. We performed all-atom molecular dynamics (MD) simulations for the initial opening process of MscL embedded in four different types of lipid bilayers with different thicknesses: 1,2-dilauroyl- sn-glycero-3-phosphocholine (DLPC)), 1,2-dimyristoyl-glycero-3-phosphorylcholine (DMPC), 1,2-dipalmitoyl- sn-glycero-3-phosphocholine (DPPC), and 1,2-distearoyl- sn-glycero-3-phosphocholine (DSPC). In response to membrane stretching, channel opening occurred only in the thinner membranes (DLPC and DMPC) in a thickness-dependent way. We found that the MscL opening was governed by the rate and degree of membrane thinning and that the channel opening was tightly associated with the tilting of transmembrane (TM) helices of MscL toward the membrane plane. Upon membrane stretching, the order parameter of acyl chains of thinner membranes (DLPC and DMPC) became smaller, whereas other thicker membranes (DPPC and DSPC) showed interdigitation with little changes in the order parameter. The decreased order parameter contributed much more to membrane thinning than did interdigitation. We conclude that the membrane-thickness-dependent MscL opening mainly arises from structural changes in MscL to match the altered membrane thickness by stretching.
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影响因子：
3.3
作者：
Klauda, Jeffery B.;Venable, Richard M.;Freites, J. Alfredo;O'Connor, Joseph W.;Tobias, Douglas J.;Mondragon-Ramirez, Carlos;Vorobyov, Igor;MacKerell, Alexander D., Jr.;Pastor, Richard W.
通讯作者：
Pastor, Richard W.
影响因子：
2.9
作者：
Moe, P;Blount, P
通讯作者：
Blount, P
影响因子：
56.9
作者：
Chang, G;Spencer, RH;Rees, DC
通讯作者：
Rees, DC
DOI：
10.1073/pnas.84.8.2297
发表时间：
1987-04-01
影响因子：
11.1
作者：
MARTINAC, B;BUECHNER, M;KUNG, C
通讯作者：
KUNG, C