Modeling Hsp70/Hsp40 interaction by multi-scale molecular simulations and co-evolutionary sequence analysis
Abstract
The interaction between the Heat Shock Proteins 70 and 40 is at the core of the ATPase regulation of the chaperone machinery that maintains protein homeostasis. However, the structural details of the interaction are still elusive and contrasting models have been proposed for the transient Hsp70/Hsp40 complexes. Here we combine molecular simulations based on both coarse-grained and atomistic models with co-evolutionary sequence analysis to shed light on this problem by focusing on the bacterial DnaK/DnaJ system. The integration of these complementary approaches resulted in a novel structural model that rationalizes previous experimental observations. We identify an evolutionarily conserved interaction surface formed by helix II of the DnaJ J-domain and a structurally contiguous region of DnaK, involving lobe IIA of the nucleotide binding domain, the inter-domain linker and the β-basket of the substrate binding domain.
Article and author information
Author details
Funding
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (2012_149278 & 20020_163042/1)
- Duccio Malinverni
- Paolo De Los Rios
Max-Planck-Gesellschaft
- Alfredo Jost Lopez
- Gerhard Hummer
Agence Nationale de la Recherche (ANR-14-ACHN-0016)
- Alessandro Barducci
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Axel T Brunger, Stanford University Medical Center, United States
Version history
- Received: November 22, 2016
- Accepted: May 10, 2017
- Accepted Manuscript published: May 12, 2017 (version 1)
- Version of Record published: July 20, 2017 (version 2)
Copyright
© 2017, Malinverni 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.
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