Nillegoda, Nadinath BStank, AntoniaMalinverni, DuccioAlberts, NielsSzlachcic, AnnaBarducci, AlessandroDe Los Rios, PaoloWade, Rebecca CBukau, Bernd2017-06-122017-06-122017-06-12201710.7554/eLife.24560https://infoscience.epfl.ch/handle/20.500.14299/138224WOS:000406840700001Hsp70 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.text::journal::journal article::research article