Statistical Thermodynamics for Functionally Rotating Mechanism of the Multidrug Efflux Transporter AcrB
Statistical Thermodynamics for Functionally Rotating Mechanism of the Multidrug Efflux Transporter AcrB
复制标题
多药外排转运蛋白 AcrB 功能旋转机制的统计热力学
DOI：
10.1021/jp5120724
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发表时间：
2015
影响因子：
3.3
通讯作者：
M. Kinoshita
中科院分区：
文献类型：
--
作者：
H. Mishima;H. Oshima;S. Yasuda;M. Kinoshita
AcrB是一种同源三聚体，是多药外排泵的关键部分。AcrB的药物转运被认为是一种“功能性旋转”的现象，但其机制尚未完全阐明。在这里，我们研究了整个功能旋转循环的能量使用我们的理论方法。我们发现AcrB的堆积效率是不均匀的，这种不均匀性主要通过溶剂熵效应起主导作用。当质子与原异构体结合或解离时，该原异构体及其两个界面的堆积性质总体上在溶剂平移熵降低的方向上受到扰动。另外两个原聚体的堆积性质，然后重组与紧密堆积的接口的恢复或维护，使溶剂熵损失可以得到补偿。由孤立的原聚体引起的功能性结构变化将导致自由能的极大增加。通过形成三聚体，任何由原聚体引起的自由能增加总是被其他两个原聚体通过上述机制引起的自由能减少所抵消。因此，功能性结构旋转是利用每个循环仅转移一个质子所产生的自由能降低来完成的。本文还讨论了与F1-ATPase的相似性。
AcrB, a homotrimer, is the pivotal part of a multidrug efflux pump. A “functionally rotating” picture has been proposed for the drug transport by AcrB, but its mechanism remains unresolved. Here, we investigate the energetics of the whole functional rotation cycle using our theoretical methods. We find that the packing efficiency of AcrB is ununiform, and this ununiformity plays imperative roles primarily through the solvent-entropy effect. When a proton binds to or dissociates from a protomer, the packing properties of this protomer and its two interfaces are perturbed overall in the direction that the solvent translational entropy is lowered. The packing properties of the other two protomers are then reorganized with the recovery or maintenance of closely packed interfaces, so that the solvent-entropy loss can be compensated. The functional structural change by an isolated protomer would cause a seriously large free-energy increase. By forming a trimer, any free-energy increase caused by a protomer is always canceled out by the free-energy decrease brought by the other two protomers via the mechanism mentioned above. The functional structural rotation is thus accomplished using the free-energy decrease arising from the transfer of only a single proton per cycle. The similarities to F1-ATPase are also discussed.