Elasticity, friction, and pathway of γ-subunit rotation in FoF1-ATP synthase
Elasticity, friction, and pathway of γ-subunit rotation in FoF1-ATP synthase
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FoF1-ATP 合酶中 γ 亚基旋转的弹性、摩擦和途径
DOI：
10.1073/pnas.1500691112
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
G. Hummer
中科院分区：
文献类型：
--
作者：
K. Okazaki;G. Hummer
FoF 1-ATP合成酶产生从细菌到人类的细胞功能所必需的ATP。其中心γ亚基的旋转将膜包埋的Fo马达中的质子转运与催化F1马达中的ATP合成偶联。为了解释其高效率，确定其最高速度，并表征其机制，我们构建了一个粘弹性模型的F1旋转电机的分子动力学模拟轨迹。我们发现，γ亚基的灵活性刚好足以补偿哺乳动物Fo和F1马达的不相称的八重和三重旋转对称性。由此产生的能量约束决定了Fo和F1旋转马达的耦合旋转的独特途径，并解释了在单分子实验中看到的精细步进。我们结合联合收割机和力学模拟来探索FoF 1-ATP合酶的耦合旋转马达的能量转换机制。考虑摩擦耗散的扭转粘弹性模型定量地再现了F1-ATPase旋转马达中扭矩驱动γ亚基旋转的原子分子动力学模拟中所见的动力学和能量学。从模拟中确定的扭转弹性系数与独立的单分子实验探测γ亚基的不同片段的结果一致，这解决了长期存在的争议。在对应于实验周转率的101 kHz的稳定转速下，计算出的每转小于kBT的摩擦耗散与完全可逆电机的高热力学效率一致。在无负载的情况下，停留之间过渡期间的最大转速达到101 MHz。能量的限制规定了一个独特的途径耦合旋转的Fo和F1旋转电机在ATP合酶，并解释需要更精细的步进F1电机在哺乳动物系统中，在最近的实验中看到的。为了分别补偿Fo和F1中的无公度八重和三重旋转对称性，很大一部分外部机械功以弹性能的形式瞬时储存在γ亚基中。这里开发的一般框架应该适用于其他分子机器。
Significance FoF1-ATP synthase produces the ATP essential for cellular functions from bacteria to humans. Rotation of its central γ-subunit couples proton translocation in the membrane-embedded Fo motor to ATP synthesis in the catalytic F1 motor. To explain its high efficiency, determine its top speed, and characterize its mechanism, we construct a viscoelastic model of the F1 rotary motor from molecular dynamics simulation trajectories. We find that the γ-subunit is just flexible enough to compensate for the incommensurate eightfold and threefold rotational symmetries of mammalian Fo and F1 motors, respectively. The resulting energetic constraints dictate a unique pathway for the coupled rotations of the Fo and F1 rotary motors, and explain the fine stepping seen in single-molecule experiments. We combine molecular simulations and mechanical modeling to explore the mechanism of energy conversion in the coupled rotary motors of FoF1-ATP synthase. A torsional viscoelastic model with frictional dissipation quantitatively reproduces the dynamics and energetics seen in atomistic molecular dynamics simulations of torque-driven γ-subunit rotation in the F1-ATPase rotary motor. The torsional elastic coefficients determined from the simulations agree with results from independent single-molecule experiments probing different segments of the γ-subunit, which resolves a long-lasting controversy. At steady rotational speeds of ∼1 kHz corresponding to experimental turnover, the calculated frictional dissipation of less than kBT per rotation is consistent with the high thermodynamic efficiency of the fully reversible motor. Without load, the maximum rotational speed during transitions between dwells is reached at ∼1 MHz. Energetic constraints dictate a unique pathway for the coupled rotations of the Fo and F1 rotary motors in ATP synthase, and explain the need for the finer stepping of the F1 motor in the mammalian system, as seen in recent experiments. Compensating for incommensurate eightfold and threefold rotational symmetries in Fo and F1, respectively, a significant fraction of the external mechanical work is transiently stored as elastic energy in the γ-subunit. The general framework developed here should be applicable to other molecular machines.
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影响因子：
14.8
作者：
Pogoryelov, Denys;Krah, Alexander;Meier, Thomas
通讯作者：
Meier, Thomas
影响因子：
3.4
作者：
Dittrich, M;Hayashi, S;Schulten, K
通讯作者：
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DOI：
10.1073/pnas.1212841109
发表时间：
2012-09-11
影响因子：
11.1
作者：
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通讯作者：
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F1-ATP 酶的不对称性及其对旋转周期的影响。
DOI：
10.1016/s0006-3495(04)74208-3
发表时间：
2004
期刊：
Biophysical journal.
影响因子：
--
作者：
Sun,SeanX;Wang,Hongyun;Oster,George
通讯作者：
Oster,George