Matthias P. Mayer
PhD 1990 University of Freiburg
Postdoctoral work at the University of Utah, Salt Lake City,
USA and the Centre Médical Universitaire Genève,
Switzerland
Project group leader since 1997 at the Institute for Biochemistry
and Molecular Biology, University of Freiburg and since 2002
at the ZMBH, University of Heidelberg.
Chaperone mediated protein folding
Current research
Inside a living cell many polypeptides need the assistance
of a set of specialized proteins, so called molecular chaperones,
in order to attain and keep their active conformation. The 70
kDa heat shock proteins (Hsp70) are a family of chaperones that
assists many folding processes including folding of newly synthesized
and stress denatured polypeptides, translocation of proteins
into organelles, assembly and disassembly of oligomeric complexes,
and control of stability and activity of regulatory proteins.
To no other group of chaperones such a wide variety of folding
tasks has been attributed. The evolutionary strategy of adaptation
to their specific functions comprise (i) structural variations
including large insertions into the substrate binding domain
leading to the Hsp110 and Hsp170 relatives, (ii) regulation by
a large number of cofactors, and (iii) cooperation with other
chaperones e.g. Hsp90s and Hsp100s. While the basic functional
cycle of the Hsp70 chaperones was elucidated to a certain degree,
little is known about the biochemical function and the physiological
role of many of the cofactors and about the integration of several
chaperones into a folding machine. In addition, the mechanistic
consequences of many of the variations within the Hsp70 structure
are poorly understood. Especially the Hsp110 and Hsp170 relatives
remained up to now enigmatic. There are indications that Hsp110
cooperate with other chaperones including Hsp70 and Hsp90 proteins
to form large molecular machines.
Contact:
Matthias P. Mayer
ZMBH
Im Neuenheimer Feld 282, D-69120 Heidelberg
Germany
Tel.: +49-6221-54 68 29
Fax: +49-6221-54 58 94
email: M.Mayer@zmbh.uni-heidelberg.de
personal home page:
http://www.zmbh.uni-heidelberg.de/Bukau/research2.html
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Projects for a doctoral thesis
Biochemical and biophysical characterization of cofactors
of the eukaryotic Hsp70 chaperones.
Identification of chaperone-binding sites and analysis of the
conformation of chaperone bound substrates using mass-spectrometry
and proton-deuterium exchange experiments.
Characterization of the ATPase cycle and the chaperone activity
of Hsp110 proteins.
Search for cooperating proteins and targeting factors of the
Hsp110 chaperones using genetic and biochemical methods.
Selected publications
Mayer, M.P., Brehmer, D., Gässler, C.S. and Bukau, B.
(2001) Hsp70 Chaperone Machines. In Horwich, A.L. (ed.) Advances
in Protein Chemistry: Protein folding in the Cell. Academic
Press, San Diego, Vol. 59, pp. 1-44.
Mayer, M.P., Schröder, H., Rüdiger, S., Paal, K., Laufen,
T. and Bukau, B. (2000) Multistep mechanism of substrate binding
determines chaperone activity of Hsp70. Nature Struct. Biol.,
7, 586-593.
Gässler, C.S., Wiederkehr, T., Brehmer, D., Bukau, B. and
Mayer, M.P. (2001) Bag-1M accelerates nucleotide release of human
Hsc70 and Hsp70 and can act concentration dependent as positive
and negative cofactor. J. Biol. Chem., 276, 32538-32544.
Kluck, C., Pazelt, H., Genevaux, P., Brehmer, D., Rist, W., Schneider-Mergener,
J., Bukau, B. and Mayer, M.P. (2002) Structure-function analysis
of HscC, the Escherichia coli member of a novel subfamily
of specialized Hsp70 chaperones. J. Biol. Chem., 277,41060-41069.
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