Functional rotation induced by alternating protonation states in the multidrug transporter AcrB: all-atom molecular dynamics simulations.
Functional rotation induced by alternating protonation states in the multidrug transporter AcrB: all-atom molecular dynamics simulations.
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DOI：
10.1021/bi400119v
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发表时间：
2013-10
期刊：
影响因子：
2.9
通讯作者：
T. Yamane;S. Murakami;M. Ikeguchi
中科院分区：
文献类型：
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作者：
T. Yamane;S. Murakami;M. Ikeguchi
在革兰氏阴性菌中，多药物转运蛋白AcrB利用质子动力作为能量来源，主动输出各种有害化合物。AcrB采用不对称结构，包括三个具有不同构象的原聚体，它们在药物输出过程中依次转化;这些在药物输出过程中的环状构象变化被称为功能旋转。为了研究质子动力驱动的功能旋转，进行了全原子分子动力学模拟。使用不同的质子化状态的跨膜结构域的中间的可滴定的残基，我们的模拟揭示了特定的质子化状态和侧链构型之间的相关性。改变Asp 408的质子化状态诱导了自发的结构转变，这表明质子易位化学计量可能是每个功能旋转循环一个质子。此外，我们的模拟表明，交替质子化状态的跨膜结构域诱导功能旋转的搬运工域，这是主要负责药物运输。
The multidrug transporter AcrB actively exports a wide variety of noxious compounds using proton-motive force as an energy source in Gram-negative bacteria. AcrB adopts an asymmetric structure comprising three protomers with different conformations that are sequentially converted during drug export; these cyclic conformational changes during drug export are referred to as functional rotation. To investigate functional rotation driven by proton-motive force, all-atom molecular dynamics simulations were performed. Using different protonation states for the titratable residues in the middle of the transmembrane domain, our simulations revealed the correlation between the specific protonation states and the side-chain configurations. Changing the protonation state for Asp408 induced a spontaneous structural transition, which suggests that the proton translocation stoichiometry may be one proton per functional rotation cycle. Furthermore, our simulations demonstrate that alternating the protonation states in the transmembrane domain induces functional rotation in the porter domain, which is primarily responsible for drug transport.