Efficient conversion of chemical energy into mechanical work by Hsp70 chaperones
Efficient conversion of chemical energy into mechanical work by Hsp70 chaperones
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DOI：
10.7554/elife.48491
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发表时间：
2019-12-17
期刊：
影响因子：
7.7
通讯作者：
Barducci, Alessandro
中科院分区：
文献类型：
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作者：
Assenza, Salvatore;Sassi, Alberto Stefano;Barducci, Alessandro
Hsp70分子伴侣是丰富的atp依赖的纳米机器，积极重塑非天然的，错误折叠的蛋白质，并协助各种基本的细胞过程。在这里，我们结合互补的理论方法来阐明伴侣诱导的底物蛋白膨胀的结构和热力学细节，特别强调ATP水解所起的关键作用。我们首先使用粗粒度分子模拟确定了由于多个伴侣结合而导致的底物膨胀的构象自由能成本。然后，我们利用这一结果来实现一个非平衡速率模型，该模型估计膨胀程度作为ATP水解提供的自由能的函数。我们的结果在定量上与最近的单分子FRET实验一致，并突出了该过程的明显非平衡性质，表明hsp70经过优化，可以有效地将化学能转化为接近生理条件的机械功。
Hsp70 molecular chaperones are abundant ATP-dependent nanomachines that actively reshape non-native, misfolded proteins and assist a wide variety of essential cellular processes. Here, we combine complementary theoretical approaches to elucidate the structural and thermodynamic details of the chaperone-induced expansion of a substrate protein, with a particular emphasis on the critical role played by ATP hydrolysis. We first determine the conformational free-energy cost of the substrate expansion due to the binding of multiple chaperones using coarse-grained molecular simulations. We then exploit this result to implement a non-equilibrium rate model which estimates the degree of expansion as a function of the free energy provided by ATP hydrolysis. Our results are in quantitative agreement with recent single-molecule FRET experiments and highlight the stark non-equilibrium nature of the process, showing that Hsp70s are optimized to effectively convert chemical energy into mechanical work close to physiological conditions.