Mechanosensitive channel MscS in the open state: modeling of the transition, explicit simulations, and experimental measurements of conductance.
Mechanosensitive channel MscS in the open state: modeling of the transition, explicit simulations, and experimental measurements of conductance.
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DOI：
10.1085/jgp.200810000
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发表时间：
2008-07
期刊：
影响因子：
--
通讯作者：
Sukharev S
中科院分区：
文献类型：
--
作者：
Anishkin A;Kamaraju K;Sukharev S
小电导机械敏感通道（MscS）是广泛存在于许多有壁细胞和一些细胞内细胞器中的膨压调节剂。大肠杆菌MscS作为张力激活的渗透压释放阀表现出不饱和的电导（1.2 nS的39 mS/cm的电解质）和弱偏好的阴离子。追求在这个通道中的过渡途径，我们应用外推运动协议（位移，最小化和短模拟周期）先前生成的紧凑的静止构象的MscS。我们观察到倾斜和矫直的扭结孔形成TM 3螺旋在桶膨胀。扩展的全原子模拟证实了在双层的开放构象的稳定性。平衡后观察到的TM 3的53°自发轴向旋转增加了孔的宽度和极性，从而允许稳定的电压非依赖性水合作用以及阳离子和阴离子在整个孔中的存在。所得的开放状态，其特征在于由1.6 nm宽的孔，满足实验电导和面内膨胀。模拟中施加的跨膜电场（±100至±200 mV）产生了K+和Cl−的流动，Cl−电流在较高电压下占主导地位。电渗透水通量与氯离子电流密切相关（每Cl−有108沃茨）。选择性和整流与在相同电压范围内进行的实验测量一致。在孔周围的带电残基中，只有K169被发现在整流中有明显的贡献。我们的结论是：（a）TM 3的桶形膨胀包括倾斜、拉直和旋转，提供了解释开孔导电性质的几何形状和静电学;（B）观察到的离子通过孔的方案类似于电扩散，因此宏观估计非常接近实验和分子动力学模拟的电导;（c）在更高电压下增加的相反离子通量的相互作用可导致比在反转电位附近测量的选择性更强的选择性。
Mechanosensitive channels of small conductance (MscS) are ubiquitous turgor pressure regulators found in many walled cells and some intracellular organelles. Escherichia coli MscS acting as a tension-activated osmolyte release valve shows a nonsaturable conductance (1.2 nS in a 39 mS/cm electrolyte) and weak preference for anions. Pursuing the transition pathways in this channel, we applied the extrapolated motion protocol (cycles of displacements, minimizations, and short simulations) to the previously generated compact resting conformation of MscS. We observed tilting and straightening of the kinked pore-forming TM3 helices during the barrel expansion. Extended all-atom simulations confirmed the stability of the open conformation in the bilayer. A 53° spontaneous axial rotation of TM3s observed after equilibration increased the width and polarity of the pore allowing for stable voltage-independent hydration and presence of both cations and anions throughout the pore. The resultant open state, characterized by a pore 1.6 nm wide, satisfied the experimental conductance and in-plane expansion. Applied transmembrane electric field (±100 to ±200 mV) in simulations produced a flow of both K+ and Cl−, with Cl− current dominating at higher voltages. Electroosmotic water flux strongly correlated with the chloride current (∼8 waters per Cl−). The selectivity and rectification were in agreement with the experimental measurements performed in the same range of voltages. Among the charged residues surrounding the pore, only K169 was found to contribute noticeably in the rectification. We conclude that (a) the barrel expansion involving tilting, straightening, and rotation of TM3s provides the geometry and electrostatics that accounts for the conductive properties of the open pore; (b) the observed regimen of ion passage through the pore is similar to electrodiffusion, thus macroscopic estimations closely approximate the experimental and molecular dynamics-simulated conductances; (c) increased interaction of the opposing ionic fluxes at higher voltages may result in selectivities stronger than measured near the reversal potential.
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影响因子：
11.4
作者：
Li, YZ;Moe, PC;Blount, P
通讯作者：
Blount, P
影响因子：
3.4
作者：
Gullingsrud, J;Schulten, K
通讯作者：
Schulten, K
影响因子：
3.4
作者：
Chiang, CS;Anishkin, A;Sukharev, S
通讯作者：
Sukharev, S
影响因子：
16.8
作者：
Edwards, MD;Li, YZ;Booth, IR
通讯作者：
Booth, IR
DOI：
10.1085/jgp.200409198
发表时间：
2005-02
期刊：
The Journal of general physiology
影响因子：
--
作者：
Akitake B;Anishkin A;Sukharev S
通讯作者：
Sukharev S