Evolution of an intricate J-protein network driving protein disaggregation in eukaryotes

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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.

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Nadinath B Nillegoda

Center for Molecular Biology, University of Heidelberg, Heidelberg, Germany

For correspondence
n.nillegoda@zmbh.uni-heidelberg.de

Competing interests
The authors declare that no competing interests exist.
Antonia Stank

Heidelberg Institute for Theoretical Studies, Heidelberg, Germany

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The authors declare that no competing interests exist.
Duccio Malinverni

Laboratory of Statistical Biophysics, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

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The authors declare that no competing interests exist.
Niels Alberts

Center for Molecular Biology, University of Heidelberg, Heidelberg, Germany

Competing interests
The authors declare that no competing interests exist.
Anna Szlachcic

Center for Molecular Biology, University of Heidelberg, Heidelberg, Germany

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The authors declare that no competing interests exist.
Alessandro Barducci

Inserm, U1054, Montpellier, France

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The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-1911-8039
Paolo De Los Rios

Laboratory of Statistical Biophysics, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland

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The authors declare that no competing interests exist.
Rebecca C Wade

Center for Molecular Biology, University of Heidelberg, Heidelberg, Germany

For correspondence
rebecca.wade@h-its.org

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The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-5951-8670
Bernd Bukau

Center for Molecular Biology, University of Heidelberg, Heidelberg, Germany

For correspondence
bukau@zmbh.uni-heidelberg.de

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-0521-7199

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.

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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.