Subsequent projects | Special projects

Start of funding 01.07.2023

Investigation of client protein transfer pathways between the Hsp70 and Hsp90 chaperone systems

Prof. Dr. Johannes Buchner
Technische Universität München
TUM School of natural Science

Prof. Dr. Judith Frydman
Stanford University
School of Humanities and Science


Molecular chaperones, supported by a plethora of co-chaperones, regulate the folding, function and quality control of proteins. The heat shock proteins (Hsp) 70 and Hsp90 cooperate to achieve client folding. The Hsp70 system has its own chaperone activity. However, a large number of client proteins depend on the transfer to Hsp90 for full activation. Several co-chaperones are known to support client protein transfer between the chaperone systems. However, there is a lack of understanding of how the different pathways are used and coordinated in parallel in the cell. In collaboration with the Frydman lab, we will use proximity ligation to generate a detailed picture of how the different client transfer pathways are organized and regulated in vivo.

Final report:
As part of the collaboration funded by BaCaTeC, we worked with Prof. Judith Frydman to successfully adapt a method developed there for labelling proteins in cells to our research questions. Both groups are interested in how protein folding is regulated in cells and, in particular, what role folding helper proteins, known as molecular chaperones, play in this process. These proteins are characterised by their ability to recognise the folding state of many different substrate proteins and support their productive folding. This project focused on the transfer of substrate proteins between the Hsp70 and Hsp90 chaperones and, in particular, on determining the influence of various co-chaperones that regulate this process. Using the approach developed in the Frydman laboratory, we were able to identify several potentially relevant Hsp70/Hsp90 transfer partners. The hits found included both known factors and unexpected interaction partners, providing new insights into the organisation of the co-chaperone network. The promising results create an important basis for further investigations that will allow the dynamics of substrate interaction in chaperone systems to be analysed in other contexts in the future.