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Small Heat shock proteins (sHsps) are a family of molecular chaperones that bind nonnative proteins in an ATP-independent manner. Caenorhabditis elegans encodes 16 different sHsps, among them Hsp17, which is evolutionarily distinct from other sHsps in the nematode. The structure and mechanism of Hsp17 and how these may differ from other sHsps remain unclear. Here, we find that Hsp17 has a distinct expression pattern, structural organization, and chaperone function. Consistent with its presence under nonstress conditions, and in contrast to many other sHsps, we determined that Hsp17 is a mono-disperse, permanently active chaperone in vitro, which interacts with hundreds of different C. elegans proteins under physiological conditions. Additionally, our cryo-EM structure of Hsp17 reveals that in the 24-mer complex, 12 N-terminal regions are involved in its chaperone function. These flexible regions are located on the outside of the spherical oligomer, whereas the other 12 N-terminal regions are engaged in stabilizing interactions in its interior. This allows the same region in Hsp17 to perform different functions depending on the topological context. Taken together, our results reveal structural and functional features that further define the structural basis of permanently active sHsps.

The Heat Shock Response (HSR) allows cells to react to a changing environment. In this work, the HSR of yeast at 37 °C, 42 °C and 46 °C was analyzed at the level of the transcriptome, translatome and proteome. It was shown that Hsf1 and Msn2/4 are the key regulators of the transcriptional HSR and that stress-induced protein turnover is replenished by increased translation up to 42 °C. In addition, a detailed structure of Hsp26 was resolved and the effects of Hsp26 phosphorylation were investigated., Die Hitzeschockantwort (HSR) ermöglicht Zellen auf eine sich verändernde Umwelt zu reagieren. In dieser Arbeit wurde die HSR von Hefe bei 37 °C, 42 °C und 46 °C auf Transkriptom-, Translatom- und Proteomebene analysiert. Es wurde gezeigt, dass Hsf1 und Msn2/4 die Schlüsselregulatoren der transkriptionellen HSR sind und, dass bis 42 °C Stress-induzierter Proteinumsatz, durch Translation ausgeglichen wird. Außerdem wurde eine hochaufgelöste Hsp26 Struktur erhalten und die Effekte der Phosphorylierung von Hsp26 untersucht.