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Elife. 2017 May 15;6. pii: e24560. doi: 10.7554/eLife.24560.

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

Author information

1
Center for Molecular Biology (ZMBH), Heidelberg University, Heidelberg, Germany.
2
DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, Germany.
3
Heidelberg Institute for Theoretical Studies, Heidelberg, Germany.
4
Heidelberg Graduate School of Mathematical and Computational Methods for the Sciences, University of Heidelberg, Heidelberg, Germany.
5
Laboratory of Statistical Biophysics, School of Basic Sciences, Institute of Physics, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
6
Inserm, U1054, Montpellier, France.
7
CNRS, UMR 5048, Centre de Biochimie Structurale, Université de Montpellier, Montpellier, France.
8
Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
9
Interdisciplinary Center for Scientific Computing, Heidelberg University, Heidelberg, Germany.

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.

KEYWORDS:

E. coli; Hsp40; Hsp70; J-protein; S. cerevisiae; biochemistry; biophysics; chaperone; evolution; protein disaggregation and refolding; structural biology

PMID:
28504929
PMCID:
PMC5542770
DOI:
10.7554/eLife.24560
[Indexed for MEDLINE]
Free PMC Article

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