Svergun Group
Small-angle X-ray scattering from macromolecular solutions
Figure 1. Four Distinct Structural Domains in Clostridium difficile Toxin B Visualized Using SAXS (Albesa-Jove et al., J. Mol. Biol. (2010) 396, 1260–1270).
Figure 2. Quaternary structure of the functional complex of frataxin bacterial orthologue (CyaY) with the proteins IscS and IscU. The SAXS-derived rigid body model was validated by NMR and sitedirected mutagenesis (Prischi et al.. Nat Commun. 2010,1, 95).
Previous and current research
Small-angle X-ray scattering (SAXS) reveals low resolution (1-2 nm) structures of biological macromolecules in close-to-native solutions for an extremely broad range of sizes, from small peptides to huge macromolecular machines and at variable conditions. For many complicated biological systems, which may be flexible or have a dynamic nature, SAXS is the only method capable of providing structural information. Recent experimental and methodical developments have significantly enhanced the resolution and reliability of the SAXS-based structural models. This versatility and universality - and the fact that it does not need crystals to characterise the structure - make SAXS an ideal tool for systems structural biology, and the last decade saw a renaissance of biological SAXS worldwide.
Our group leads the development of novel computational methods for constructing 3D structural models from the scattering data. Special attention is given to the joint use of SAXS with other structural, biophysical and biochemical techniques including macromolecular crystallography, NMR, electron microscopy, neutron scattering and bioinformatics. We developed the world’s most used SAXS data analysis program package, ATSAS, which is employed in over 1300 laboratories, and we continue providing the scientific community with novel approaches.
We run a synchrotron beamline, X33, dedicated to biological solution SAXS at DESY’s storage ring, DORIS III. The rapidly-growing demand for SAXS in the biological community has led to a more than six-fold increase in the user demand at X33 during the last decade. X33 is the first synchrotron SAXS beamline with a robotic sample changer and a data analysis pipeline for building structural models online, with FedEx-style and remote data access options. All the X33 developments are being ported to the new high brilliance BioSAXS beamline, which is a presently under commissioning at the third-generation PETRA III storage ring at DESY. Most of the external users of X33 are seeking collaborative projects where the SAXS group members help not only with data collection but also with analysis. In numerous exciting applications, SAXS is employed to study domain structure of individual macromolecules (figure 1), conformational transitions (e.g. upon ligand binding), quaternary structure of complexes (figure 2), but also oligomeric mixtures, intrinsically unfolded proteins, hierarchical systems and other objects of high biological and medical importance.
Future projects and goals
The present and future work of the group includes:
- Further development of novel methods and approaches for the reconstruction of tertiary and quaternary structure of macromolecules and complexes from X-ray and neutron scattering data;
- the use of bioinformatic to construct and validate SAXS-based models and the joint applications of SAXS with crystallography, NMR, electron microscopy and other methods;
- participation in collaborative projects at the X33 beamline, employing SAXS to study the structure of a wide range of biological systems in solution;
- complete automation of a biological SAXS experiment and data analysis at X33, and, in collaboration with the PETRA III group, at the new high-brilliance BioSAXS beamline.