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 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
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.
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
-
- 2,265
- views
-
- 325
- downloads
-
- 26
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
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)
Further reading
-
- Physics of Living Systems
We use data from 30 countries and find that the more women in a discipline, the lower quality the research in that discipline is evaluated to be and the lower the funding success rate is. This affects men and women, and is robust to age, number of research outputs, and bibliometric measures where such data are available. Our work builds on others’ findings that women’s work is valued less, regardless of who performs that work.
-
- Microbiology and Infectious Disease
- Physics of Living Systems
Filamentous multicellular cable bacteria perform centimeter-scale electron transport in a process that couples oxidation of an electron donor (sulfide) in deeper sediment to the reduction of an electron acceptor (oxygen or nitrate) near the surface. While this electric metabolism is prevalent in both marine and freshwater sediments, detailed electronic measurements of the conductivity previously focused on the marine cable bacteria (Candidatus Electrothrix), rather than freshwater cable bacteria, which form a separate genus (Candidatus Electronema) and contribute essential geochemical roles in freshwater sediments. Here, we characterize the electron transport characteristics of Ca. Electronema cable bacteria from Southern California freshwater sediments. Current–voltage measurements of intact cable filaments bridging interdigitated electrodes confirmed their persistent conductivity under a controlled atmosphere and the variable sensitivity of this conduction to air exposure. Electrostatic and conductive atomic force microscopies mapped out the characteristics of the cell envelope’s nanofiber network, implicating it as the conductive pathway in a manner consistent with previous findings in marine cable bacteria. Four-probe measurements of microelectrodes addressing intact cables demonstrated nanoampere currents up to 200 μm lengths at modest driving voltages, allowing us to quantify the nanofiber conductivity at 0.1 S/cm for freshwater cable bacteria filaments under our measurement conditions. Such a high conductivity can support the remarkable sulfide-to-oxygen electrical currents mediated by cable bacteria in sediments. These measurements expand the knowledgebase of long-distance electron transport to the freshwater niche while shedding light on the underlying conductive network of cable bacteria.