Header

UZH-Logo

Maintenance Infos

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.

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.

Statistics

Citations

Dimensions.ai Metrics
20 citations in Web of Science®
19 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

23 downloads since deposited on 12 Feb 2020
3 downloads since 12 months
Detailed statistics

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:27 Jan 2022 01:05
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
  • Content: Published Version
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)