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