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Biologische Systeme und Medizin Vortrag: Fr., 10:00–10:20 F-V56
Concepts and highlights in structural biology at EMBL-Hamburg: towards
future applications at PETRA-III
Stefan Fiedler 1 , Manfred Weiss 1 , Manfred Roessle 1 , Dmitri Svergun 1 ,
Christoph Hermes 1 , Matthias Wilmanns 1
1 European Molecular Biology Laboratory, Hamburg Unit c/o DESY, Notkestr. 85,
D-22603 Hamburg, Germany
An important development in structural biology is the investigation of macromolecular
complexes of increasing size such as the molecular architecture of muscle sarcomeres.
At the EMBL Hamburg Unit it has been possible to determine the structure of the
N-terminal assembly complex of titin, the largest gene product of the human genome,
which comprises up to 38,000 residues in its largest isoform.
Structural proteomics projects like the Mtb initiative, coordinated by our institute,
form another trend. This initiative is targeting proteins from the Mycobacterium tuberculosis
and is aiming to identify novel lead compounds to combat tuberculosis. Such
projects call for high-throughput techniques and integrated approaches including X-ray
crystallography and X-ray small angle scattering.
These developments are reflected in our concept for an Integrated Life Science Centre
built and operated by the EMBL at PETRA-III, the planned 3rd generation synchrotron
on the DESY site in Hamburg. The centre will comprise two beamlines for
Macromolecular X-ray crystallography (MX) and one for Small Angle X-ray Scattering
(SAXS) all linked through a joint sample preparation and storage facility.
One of the MX beamlines will be dedicated to experimental phase determination over
a broad energy range, the other optimised for measurements of protein crystals with
micrometer size scattering volume. The main focus of the SAXS beamline will be
the study of protein solutions with ultra-small volume or concentration and kinetic
experiments.
The beamlines will be integrated into a highly automated pipeline ranging from biophysical
and biochemical protein characterisation to high throughput crystallisation,
automated crystal mounting, centering, data collection and data interpretation allowing
large numbers of samples to be investigated. The automation of most of these steps
is being tested and implemented already at the existing facilities at the DORIS storage
ring.
We expect to make the facilities successively available to the international scientific
community with the planned beginning of user operation of PETRA-III in 2009.