Efficient conversion of chemical energy into mechanical work by Hsp70 chaperones
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.
Keywords
Cite
@article{arxiv.1902.01612,
title = {Efficient conversion of chemical energy into mechanical work by Hsp70 chaperones},
author = {Salvatore Assenza and Alberto S. Sassi and Ruth Kellner and Ben Schuler and Paolo De Los Rios and Alessandro Barducci},
journal= {arXiv preprint arXiv:1902.01612},
year = {2019}
}