Efficient conversion of chemical energy into mechanical work by Hsp70 chaperones

  1. Salvatore Assenza
  2. Alberto Stefano Sassi
  3. Ruth Kellner
  4. Benjamin Schuler
  5. Paolo De Los Rios
  6. Alessandro Barducci  Is a corresponding author
  1. ETH Zürich, Switzerland
  2. École Polytechnique Fédérale de Lausanne, Switzerland
  3. University of Zurich, Switzerland
  4. 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

  1. Salvatore Assenza

    Laboratory of Food and Soft Materials, ETH Zürich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  2. Alberto Stefano Sassi

    Institute of Physics, School of Basic Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Ruth Kellner

    Department of Biochemistry, University of Zurich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  4. Benjamin Schuler

    Department of Biochemistry, University of Zurich, Zurich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5970-4251
  5. Paolo De Los Rios

    Institute of Physics, School of Basic Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5394-5062
  6. Alessandro Barducci

    Centre de Biochimie Structurale U1054, INSERM, Montpellier, France
    For correspondence
    alessandro.barducci@cbs.cnrs.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1911-8039

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

  1. Arup K Chakraborty, Massachusetts Institute of Technology, United States

Version history

  1. Received: May 15, 2019
  2. Accepted: December 17, 2019
  3. Accepted Manuscript published: December 17, 2019 (version 1)
  4. 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

  • 2,228
    views
  • 324
    downloads
  • 22
    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)

  1. Salvatore Assenza
  2. Alberto Stefano Sassi
  3. Ruth Kellner
  4. Benjamin Schuler
  5. Paolo De Los Rios
  6. Alessandro Barducci
(2019)
Efficient conversion of chemical energy into mechanical work by Hsp70 chaperones
eLife 8:e48491.
https://doi.org/10.7554/eLife.48491

Share this article

https://doi.org/10.7554/eLife.48491

Further reading

    1. Physics of Living Systems
    Giulio Facchini, Alann Rathery ... Andrea Perna
    Research Article

    Termites build complex nests which are an impressive example of self-organization. We know that the coordinated actions involved in the construction of these nests by multiple individuals are primarily mediated by signals and cues embedded in the structure of the nest itself. However, to date there is still no scientific consensus about the nature of the stimuli that guide termite construction, and how they are sensed by termites. In order to address these questions, we studied the early building behavior of Coptotermes gestroi termites in artificial arenas, decorated with topographic cues to stimulate construction. Pellet collections were evenly distributed across the experimental setup, compatible with a collection mechanism that is not affected by local topography, but only by the distribution of termite occupancy (termites pick pellets at the positions where they are). Conversely, pellet depositions were concentrated at locations of high surface curvature and at the boundaries between different types of substrate. The single feature shared by all pellet deposition regions was that they correspond to local maxima in the evaporation flux. We can show analytically and we confirm experimentally that evaporation flux is directly proportional to the local curvature of nest surfaces. Taken together, our results indicate that surface curvature is sufficient to organize termite building activity and that termites likely sense curvature indirectly through substrate evaporation. Our findings reconcile the apparently discordant results of previous studies.

    1. Microbiology and Infectious Disease
    2. Physics of Living Systems
    Fabien Duveau, Céline Cordier ... Pascal Hersen
    Research Article

    Natural environments of living organisms are often dynamic and multifactorial, with multiple parameters fluctuating over time. To better understand how cells respond to dynamically interacting factors, we quantified the effects of dual fluctuations of osmotic stress and glucose deprivation on yeast cells using microfluidics and time-lapse microscopy. Strikingly, we observed that cell proliferation, survival, and signaling depend on the phasing of the two periodic stresses. Cells divided faster, survived longer, and showed decreased transcriptional response when fluctuations of hyperosmotic stress and glucose deprivation occurred in phase than when the two stresses occurred alternatively. Therefore, glucose availability regulates yeast responses to dynamic osmotic stress, showcasing the key role of metabolic fluctuations in cellular responses to dynamic stress. We also found that mutants with impaired osmotic stress response were better adapted to alternating stresses than wild-type cells, showing that genetic mechanisms of adaptation to a persistent stress factor can be detrimental under dynamically interacting conditions.