Christoph Ratzke

German

My project focuses on the investigation of the chaperone Hsp90 with single molecule spectroscopy. Hsp90 is a very frequent chaperone which can maintain cellular integrity after heat shock. In addition, it has important functions in the unstressed cell like processing of proteins that are involved in signal transduction and cell proliferation. Since some of these proteins are involved in the formation of cancer Hsp90 became an important drug target.

Investigations of Hsp90 done in bulk so far let assume that the mechanism this protein is quite complex. Since ensemble measurements result only in average values we observe Hsp90 on the single molecule level which allows to estimate distributions of values, rare events and the estimation of single rate constants even in complex systems. The main goal of my work is the investigation of the interaction of Hsp90 with different ligands. To detect interaction events we use the fluorescence resonance energy transfer between fluorophores that have been attached to Hsp90 and its ligand. Upon binding of the ligand an energy transfer between the two labels takes place which leads to a change in the energy of the emitted fluorescence light. Detecting this change one obtains the binding dynamics.

With this technique I want to investigate the binding of ATP and different cochaperones which modify the function of Hsp90. In future I am especially interested in the interplay between different binding partners.

C. Ratzke, F. Berkemeier,T. Hugel:
"Hsp90’s mechano-chemical cycle is dominated by thermal fluctuations"
PNAS 109:161-166 (2012)

C. Ratzke, M. Mickler, B. Hellenkamp, J. Buchner and T. Hugel:
"Dynamics of heat shock protein 90 C-terminal dimerization is an important part of its conformational cycle"
PNAS, Online Early Edition in the week of August 23, 2010

M. Mickler, M. Hessling, C. Ratzke, J. Buchner and T. Hugel:
"The large conformational changes of Hsp90 are only weakly coupled to ATP hydrolysis"
Nature Structural & Molecular Biology 16, 281 - 286 (2009)