Resolving the Negative Potential Side (n-side) Water-accessible Proton Pathway of F-type ATP Synthase by Molecular Dynamics Simulations
Resolving the Negative Potential Side (n-side) Water-accessible Proton Pathway of F-type ATP Synthase by Molecular Dynamics Simulations
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DOI：
10.1074/jbc.m112.398396
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发表时间：
2012-10-19
影响因子：
4.8
通讯作者：
Groth, Georg
中科院分区：
文献类型：
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作者：
Gohlke, Holger;Schlieper, Daniel;Groth, Georg
F1 Fo-ATP合成酶的旋转是由穿过能量转换膜的质子动力驱动的。蛋白质复合物的功能就像一个涡轮机;质子流驱动跨膜F-o结构域的C环旋转，该结构域与产生ATP的F-1结构域偶联。发夹结构的c-原聚体通过保守的Asp/Glu在外跨膜螺旋（TMH）处的可逆质子化/去质子化来运输质子。一个悬而未决的问题是质子转移途径通过膜在原子分辨率。质子被认为是通过两个半通道转移到膜中间的保守cAsp/Glu和从膜中间的保守cAsp/Glu转移。通过分子动力学模拟脂双层中的C环结构，我们将水通道映射为半通道之一。我们还分析了抑制突变体cP 24 D/E61 G，其中功能性羧酸转移到c-原聚体的内部TMH。目前的模型集中在保守的羧酸侧链的“锁定”和“开放”构象无法解释这种突变体的分子功能。我们的分子动力学模拟揭示了一个扩展的水通道，额外的水分子桥接外部到内部TMH的距离。我们认为，水通道的几何形状是F1 Fo-ATP合酶的膜部分的分子功能的一个重要特征。质子通路的倾斜隔离了两个半通道，并可能有助于ATP合成模式中有利的顺时针旋转。
The rotation of F1Fo-ATP synthase is powered by the proton motive force across the energy-transducing membrane. The protein complex functions like a turbine; the proton flow drives the rotation of the c-ring of the transmembrane F-o domain, which is coupled to the ATP-producing F-1 domain. The hairpin-structured c-protomers transport the protons by reversible protonation/deprotonation of a conserved Asp/Glu at the outer transmembrane helix (TMH). An open question is the proton transfer pathway through the membrane at atomic resolution. The protons are thought to be transferred via two half-channels to and from the conserved cAsp/Glu in the middle of the membrane. By molecular dynamics simulations of c-ring structures in a lipid bilayer, we mapped a water channel as one of the half-channels. We also analyzed the suppressor mutant cP24D/E61G in which the functional carboxylate is shifted to the inner TMH of the c-protomers. Current models concentrating on the "locked" and "open" conformations of the conserved carboxylate side chain are unable to explain the molecular function of this mutant. Our molecular dynamics simulations revealed an extended water channel with additional water molecules bridging the distance of the outer to the inner TMH. We suggest that the geometry of the water channel is an important feature for the molecular function of the membrane part of F1Fo-ATP synthase. The inclination of the proton pathway isolates the two half-channels and may contribute to a favorable clockwise rotation in ATP synthesis mode.