Many protein folding processes in the cell, in particular in signal transduction cascades controlling cell homeostasis, cell cycle and apoptosis, are dependent on the assistance by molecular chaperones of the Hsp70 and Hsp90 families. Thereby dynamic high molecular weight complexes are formed between the substrate proteins and the chaperones together with a number of co-chaperones. On one hand, the substrates are thus kept in an inactive state, on the other hand, the interaction with the chaperones is essential for subsequent activation of the substrate through the signaling cascades. The central question in this process is how Hsp70 and Hsp90 control the activity of their substrates; to which extent the chaperones influence the conformation of their substrates, how the chaperones prevent dimerization and nuclear localization and how they are able to modulate posttranslational modifications like phosphorylation.

To answer these questions we analyze the molecular mechanism of Hsp70 and Hsp90 chaperone systems. We investigate how the activity of the chaperones is regulated by co-chaperones and which conformational changes in chaperones and substrate proteins are necessary to reach the active state. For these studies we use biochemical and biophysical techniques including fluorescence spectroscopy, circular dichroism spectroscopy, surface plasmon resonance spectroscopy and amide hydrogen (1H/2H)-exchange in combination with high-resolution mass spectrometry.

Selected Publications

Rist, W., Graf, C., Bukau, B., and Mayer, M. P. (2006). Amide hydrogen exchange reveals conformational changes in Hsp70 chaperones important for allosteric regulation. J Biol Chem. in press

Vogel, M., Bukau, B., and Mayer, M. P. (2006). Allosteric regulation of Hsp70 chaperones by a proline switch. Mol Cell 21, 359-367.

Rist, W., Rodriguez, F., Jorgensen, T. J., and Mayer, M. P. (2005). Analysis of subsecond protein dynamics by amide hydrogen exchange and mass spectrometry using a quenched-flow setup. Protein Sci 14, 626-632.

Mayer, M. P. (2005). Recruitment of Hsp70 chaperones: a crucial part of viral survival strategies. Rev Physiol Biochem Pharmacol 153, 1-46.

Mayer, M. P., and Bukau, B. (2005). Hsp70 chaperones: Cellular functions and molecular mechanism. Cell Mol Life Sci 62, 670-684.