Postdoc in the group of Jeff Gore, MIT
PhD student in the group of Prof. Thorsten Hugel, TU Munich
2006 - 2008
Master of Science in Biochemistry, TU Munich
2005 - 2006
Bachelor of Science in Biochemistry, TU München
2003 - 2005
Grundstudium in Biochemistry, Universität Regensburg
Scholarship of the IDK-NBT (Elitenetwork of Bavaria)
My project was focused on the investigation of the chaperone Hsp90 with single molecule spectroscopy, especially single molecule three and four color FRET. 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 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 was the investigation of the interaction of Hsp90 with different ligands. To detect interaction events I used 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. Extending this technique to three and four dyes (single molecule three/four color FRET) the simultaneous interaction with different ligands at the same time can be studied.
In this way I investigated the conformational changes of Hsp90 and its coupling to ATP turnover. With four color FRET additionally the binding of a cochaperone and its influence upon the Hsp90-ATP machinery could be studied. Thus multicolor single molecule FRET allowed to observe the dynamics in a protein complex not accessible with other techniques.
C. Ratzke, M. N.T. Nguyen, M. P. Mayer, T. Hugel:
"From a Ratchet Mechanism to Random Fluctuations Evolution of Hsp90's Mechanochemical Cycle"
JMB 423(3):462-471 (2012)
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)
Recent research and actualized publication list can be found at:
Christoph Ratzke: Ecological systems biology and multicolor FRET