Figure 1: A new data analysis tool: Correlation Map (Franke, Jeffries & Svergun, 2015).
Figure 2: SasG Protein from Staphylococcus aureus (Gruszka et al., 2015).
The Svergun group places special emphasis on hybrid approaches combining SAXS with X-ray crystallography, NMR spectroscopy and computational methods to elucidate macromolecular structure and conformational transitions in solution.
Previous and current research
Small-angle X-ray scattering (SAXS) reveals low-resolution (1-2 nm) structures of biological macromolecules and functional complexes in solution. Recent experimental and methodical developments have significantly enhanced the resolution and reliability of the SAXS-based structural models, and the last decade saw a renaissance of biological SAXS worldwide.
Our group leads the development of novel computational methods for constructing structural models from the scattering data. Special attention is given to the joint use of SAXS with other methods including crystallography, NMR, electron microscopy and bioinformatics. We developed the world’s most used programme package, ATSAS, employed by more than 10,000 users from more than 50 countries.
Our group runs a dedicated high brilliance synchrotron beamline P12 at DESY’s third generation storage ring, PETRA III. P12 has a robotic sample changer for rapid automated experiments, and possesses a data analysis pipeline for building structural models online. The beamline offers FedEx-style and remote data access options, as well as an in-line purification and biophysical characterisation setup using size exclusion chromatography (Malvern).
In collaborative projects, group members help users not only with data collection, but also with structural modelling. SAXS is employed to study overall structural organisation of macromolecules and conformational transitions and to quantitatively characterise oligomeric mixtures, intrinsically unfolded proteins, hierarchical systems and other objects of high biological and medical importance. Figure 1 illustrates the study of the structure and regulation of human muscle α-Actinin by a combination of crystallography and SAXS. Molecular modelling revealed structural flexibility is essential for the crosslinking of antiparallel F-actin.
In 2014, the group launched a Small Angle Scattering Biological Data Bank (figure 2), a curated repository for small angle X-ray and neutron scattering data and models for the biological community.
Future projects and goals
- Further methods development for the reconstruction of macromolecular structure from X-ray and neutron scattering.
- Hybrid applications of SAXS with crystallography, NMR, electron microscopy and bioinformatics to construct and validate structural models.
- Participation in collaborative SAXS projects at the P12 beamline.
- Further extension of P12 including time-resolved and anomalous scattering approaches.