Evolution of an intricate J-protein network driving protein disaggregation in eukaryotes
- University of Heidelberg, Germany
- Heidelberg Institute for Theoretical Studies, Germany
- École Polytechnique Fédérale de Lausanne, Switzerland
- Inserm, U1054, France
Abstract
Hsp70 participates in a broad spectrum of protein folding processes extending from nascent chain folding to protein disaggregation. This versatility in function is achieved through a diverse family of J-protein cochaperones that select substrates for Hsp70. Substrate selection is further tuned by transient complexation between different classes of J-proteins, which expands the range of protein aggregates targeted by metazoan Hsp70 for disaggregation. We assessed the prevalence and evolutionary conservation of J-protein complexation and cooperation in disaggregation. We find the emergence of a eukaryote-specific signature for interclass complexation of canonical J-proteins. Consistently, complexes exist in yeast and human cells, but not in bacteria, and correlate with cooperative action in disaggregation in vitro. Signature alterations exclude some J-proteins from networking, which ensures correct J-protein pairing, functional network integrity and J-protein specialization. This fundamental change in J-protein biology during the prokaryote-to-eukaryote transition allows for increased fine-tuning and broadening of Hsp70 function in eukaryotes.
Article and author information
Author details
Alessandro Barducci
Funding
Deutsche Forschungsgemeinschaft (SFB1036 BU617/19-3)
- Bernd Bukau
Alexander von Humboldt-Stiftung (NA)
- Nadinath B Nillegoda
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Nillegoda 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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Evolution of an intricate J-protein network driving protein disaggregation in eukaryotes
eLife 6:e24560.
https://doi.org/10.7554/eLife.24560
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