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arXiv · 1902.01612

Efficient conversion of chemical energy into mechanical work by Hsp70 chaperones

Salvatore Assenza·Alberto S. Sassi·Ruth Kellner·Ben Schuler·Paolo De Los Rios·Alessandro Barducci
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Abstract

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 computational/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 convert effectively chemical energy into mechanical work close to physiological conditions.

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Salvatore Assenza, Alberto S. Sassi, Ruth Kellner, Ben Schuler, Paolo De Los Rios, Alessandro Barducci. 2019-03-29. Efficient conversion of chemical energy into mechanical work by Hsp70 chaperones. https://arxiv.org/abs/1902.01612

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