SAS Studies of Biological Macromolecules in Solution

[AL]

Svergun, D. I. & Koch, M. H. J.
Small-Angle Scattering Studies of Biological Macromolecules in Solution
©2003 IOP Publishing Ltd.

Small-angle scattering (SAS) of x-rays and neutrons is a fundamental tool in the study of biological macromolecules. The major advantage of the method lies in its ability to provide structural information about partially or completely disordered systems. SAS allows one to study the structure of native particles in near physiological environments and to analyse structural changes in response to variations in external conditions.

In this review we concentrate on SAS studies of isotropic systems, in particular, solutions of biological macromolecules, an area where major progress has been achieved during the last decade. Solution scattering studies are especially important, given the challenge of the ‘post-genomic’ era with vast numbers of protein sequences becoming available. Numerous structural initiatives aim at large-scale expression and purification of proteins for subsequent structure determination using x-ray crystallography and NMR spectroscopy. Because of the requirement of good crystals for crystallography and the low molecular mass requirement of NMR, a significant fraction of proteins cannot be analysed using these two high-resolution methods. Progress in SAS instrumentation and novel analysis methods, which substantially improve the resolution and reliability of the structural models, makes the method an important complementary tool for these initiatives.

The review covers the basics of x-ray and neutron SAS, instrumentation, mathematical methods used in data analysis and major modelling techniques. Examples of applications of SAS to different types of biomolecules (proteins, nucleic acids, macromolecular complexes, polyelectrolytes) are presented. A brief account of the new opportunities offered by third and fourth generation synchrotron radiation sources (time-resolved studies, coherent scattering and single molecule scattering) is also given.

[Hayds]

Hi all, shameless plug for the new review from the Hamburg SAXS group:

Mertens H. D. T. & Svergun D.I.
Structural characterization of proteins and complexes using small-angle X-ray solution scattering
J Struct Biol. 2010 Oct;172(1):128-41.

Small-angle scattering of X-rays (SAXS) is an established method for the low-resolution structural characterization of biological macromolecules in solution. The technique provides three-dimensional low-resolution structures, using ab initio and rigid body modeling, and allow one to assess the oligomeric state of proteins and protein complexes. In addition, SAXS is a powerful tool for structure validation and the quantitative analysis of flexible systems, and is highly complementary to the high resolution methods of X-ray crystallography and NMR. At present, SAXS analysis methods have reached an advanced state, allowing for automated and rapid characterization of protein solutions in terms of low-resolution models, quaternary structure and oligomeric composition. In this communication, main approaches to the characterization of proteins and protein complexes using SAXS are reviewed. The tools for the analysis of proteins in solution are presented, and the impact that these tools have made in modern structural biology is discussed.