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Efficient conversion of chemical energy into mechanical work by Hsp70 chaperones

Assenza, Salvatore; Sassi, Alberto Stefano; Kellner, Ruth; Schuler, Benjamin; De Los Rios, Paolo; Barducci, Alessandro (2019). Efficient conversion of chemical energy into mechanical work by Hsp70 chaperones. eLife, 8:e48491.

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 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.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Department of Biochemistry
07 Faculty of Science > Department of Biochemistry
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Life Sciences > General Neuroscience
Life Sciences > General Immunology and Microbiology
Life Sciences > General Biochemistry, Genetics and Molecular Biology
Language:English
Date:17 December 2019
Deposited On:12 Feb 2020 11:28
Last Modified:23 Oct 2024 01:36
Publisher:eLife Sciences Publications Ltd.
ISSN:2050-084X
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.7554/eLife.48491
PubMed ID:31845888
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  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)

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