of the Max - MDC

Structural and Functional Genomics
Coordinator: Udo Heinemann
Macromolecular Structure
and Interaction
Udo Heinemann
The inner workings of the cells forming healthy or diseased organisms are governed by the interplay
of thousands of large and small molecules. The activities of these molecules – proteins,
nucleic acids, carbohydrates, lipids, membranes and small metabolites – are tightly regulated in time
and space. They can be described according to the concept of functional modules: defined units of
cellular activity that assemble into discrete, stable entities during function and often undergo cyclic
structural rearrangements. A functional module is characterized by its supra-molecular architecture
and the time domain within which it functions. It receives a specific input and delivers an appropriate
output to the cell. Some functional modules are best described as molecular machines, whereas
others are characterized by a dynamic assembly and disassembly of their constituent parts. Our laboratory
focuses on structural analyses of functional modules using macromolecular crystallography as
its central method. This approach implies that we primarily address the lower levels of modular
organization which carry out molecular and sub-modular functions. Structural data must be combined
with time-resolved functional analyses and theory to yield proper insight into modular function.
Structural proteomics
Ulf Lenski, Yvette Roske, Jörg Schulze, Anja Schütz
Within a Berlin-area structural proteomics project, more
than 500 human genes were cloned into more than 1400
Escherichia coli expression vectors, and more than 100 proteins
were purified for biophysical and structural studies.
This public catalogue of expression clones constitutes an
important resource for our structural studies. In collaboration
with the laboratory of K. Büssow (Helmholtz-Zentrum
für Infektionsforschung, HZI, Braunschweig) the methodology
used in generating this resource has been extended to
the expression cloning and purification of protein complexes
containing, in principle, an unlimited number of different
subunits. These complexes may have properties of functional
modules or sub-modules.
The available methods for the production of single recombinant
proteins or protein complexes provide the basis for the
recently established Helmholtz Protein Sample Production
Facility (Helmholtz PSPF). In a collaborative effort of MDC
and HZI, the Helmholtz PSPF (www.pspf.de) develops and
applies methods for protein sample production in various
hosts and at elevated throughput which are available to
interested researchers from Helmholtz centers and other
basic science institutions.
Intracellular signaling and cell proliferation
control
Sarbani Bhattacharya, Kerstin Böhm, Jürgen J. Müller,
Jörg Schulze
The growth arrest and DNA damage responsive protein
GADD45γ is a member of a small group of human proteins
that play an important role in cell growth and proliferation
regulation with specific functions in cell cycle control, MAPK
signalling, apoptosis and immune responses. As the related
Cancer Research 109