Efficient conversion of chemical energy into mechanical work by Hsp70 chaperones
- ETH Zürich, Switzerland
- École Polytechnique Fédérale de Lausanne, Switzerland
- University of Zurich, Switzerland
- INSERM, France
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.
Data availability
All the source data used for generating relevant figures (Fig1,2,2Supp1,4,5,6,1App) have been provided as supporting files.All the information necessary for reproducing the molecular simulations have been deposited in github (https://github.com/saassenza/Hsp70Unfoldase) and PLUMED NEST (plumID:19.076) repositories.
Article and author information
Author details
Alessandro Barducci
Funding
Agence Nationale de la Recherche (ANR-14-ACHN-0016)
- Alessandro Barducci
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (200020_163042)
- Paolo De Los Rios
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Arup K Chakraborty, Massachusetts Institute of Technology, United States
Version history
- Received: May 15, 2019
- Accepted: December 17, 2019
- Accepted Manuscript published: December 17, 2019 (version 1)
- Version of Record published: February 4, 2020 (version 2)
Copyright
© 2019, Assenza et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 2,237
- views
-
- 324
- downloads
-
- 26
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Efficient conversion of chemical energy into mechanical work by Hsp70 chaperones
eLife 8:e48491.
https://doi.org/10.7554/eLife.48491
Further reading
-
- Physics of Living Systems
Eukaryotes swim with coordinated flagellar (ciliary) beating and steer by fine-tuning the coordination. The model organism for studying flagellate motility, Chlamydomonas reinhardtii, employs synchronous, breaststroke-like flagellar beating to swim, and it modulates the beating amplitudes differentially to steer. This strategy hinges on both inherent flagellar asymmetries (e.g. different response to chemical messengers) and such asymmetries being effectively coordinated in the synchronous beating. In C. reinhardtii, the synchrony of beating is known to be supported by a mechanical connection between flagella; however, how flagellar asymmetries persist in the synchrony remains elusive. For example, it has been speculated for decades that one flagellum leads the beating, as its dynamic properties (i.e. frequency, waveform, etc.) appear to be copied by the other one. In this study, we combine experiments, computations, and modeling efforts to elucidate the roles played by each flagellum in synchronous beating. With a non-invasive technique to selectively load each flagellum, we show that the coordinated beating essentially only responds to load exerted on the cis flagellum; and that such asymmetry in response derives from a unilateral coupling between the two flagella. Our results highlight a distinct role for each flagellum in coordination and have implication for biflagellates’ tactic behaviors.
-
- Developmental Biology
- Physics of Living Systems
Geometric criteria can be used to assess whether cell intercalation is active or passive during the convergent extension of tissue.
