On the Question of Hydronium Binding to ATP-Synthase Membrane Rotors
On the Question of Hydronium Binding to ATP-Synthase Membrane Rotors
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DOI：
10.1016/j.bpj.2010.07.046
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发表时间：
2010-10-06
影响因子：
3.4
通讯作者：
Faraldo-Gomez, Jose D.
中科院分区：
文献类型：
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作者：
Leone, Vanessa;Krah, Alexander;Faraldo-Gomez, Jose D.
最近确定的原子结构的H+耦合ATP合酶膜转子已经恢复了长期存在的问题，质子是否可以绑定到这些结构的形式的水合氢离子。使用经典和量子力学模拟，我们表明，这一概念是难以置信的。结合位点的从头算分子动力学模拟表明，推定的H3O+在飞秒内去质子化。因此，结合质子不可逆地转移到所有ATP合酶转子的离子结合位点中发现的羧酸侧链。这一结果与磷脂膜中转子在100纳秒时间尺度上的经典模拟一致。这些模拟表明，在晶体结构中看到的氢键网络是不相容的束缚水合氢离子。所观察到的配位几何形状示出对应于质子化羧酸盐和结合水分子。总之，这项研究强调了这样一个概念，即结合和瞬时存储的质子在膜转子的ATP酶发生通过一个共同的化学机制，即羧酸质子化。
A recently determined atomic structure of an H+-coupled ATP-synthase membrane rotor has revived the long-standing question of whether protons may be bound to these structures in the form of a hydronium ion. Using both classical and quantum-mechanical simulations, we show that this notion is implausible. Ab initio molecular dynamics simulations of the binding site demonstrate that the putative H3O+ deprotonates within femtoseconds. The bound proton is thus transferred irreversibly to the carboxylate side chain found in the ion-binding sites of all ATP-synthase rotors. This result is consistent with classical simulations of the rotor in a phospholipid membrane, on the 100-nanosecond timescale. These simulations show that the hydrogen-bond network seen in the crystal structure is incompatible with a bound hydronium. The observed coordination geometry is shown to correspond instead to a protonated carboxylate and a bound water molecule. In conclusion, this study underscores the notion that binding and transient storage of protons in the membrane rotors of ATP synthases occur through a common chemical mechanism, namely carboxylate protonation.