Seminar

Structure analysis of biological macromolecules in solution by synchrotron small angle X-ray scattering

Dmitry Svergun, PhD

Small-angle X-ray scattering (SAXS) experiences a renaissance in the studies of macromolecular solutions allowing one to study the structure of native particles and complexes and to rapidly analyze structural changes in response to variations in external conditions. Novel data analysis methods significantly enhanced resolution and reliability of structural models provided by the technique. Emerging automation of the experiment, data processing and interpretation make solution SAXS a streamline tool for large scale structural studies in molecular biology. The method provides low resolution macromolecular shapes ab initio and is readily combined with other structural (most notably, crystallography and NMR), biophysical and biochemical techniques in multidisciplinary studies. In particular, rapid validation of predicted or experimentally obtained high resolution models in solution, identification of biologically active oligomers and addition of missing fragments to high resolution models are possible. For macromolecular complexes, quaternary structure is analyzed by rigid body movements/rotations of individual subunits. Recent developments made it possible also to quantitatively characterize flexible macromolecular systems, including intrinsically unfolded proteins. The novel methods will be illustrated by advanced applications to solutions of biological macromolecules including the joint use of SAXS with macromolecular crystallography and NMR.