PSI Structural Biology Knowledgebase

PSI | Structural Biology Knowledgebase
Header Icons

Related Articles
Signaling: A Platform for Opposing Functions
May 2015
Protein Folding and Misfolding: It's the Journey, Not the Destination
March 2015
Molecular Portraits of the Cell
February 2015
Nuclear Pore Complex: A Flexible Transporter
February 2015
Nuclear Pore Complex: Higher Resolution of Macromolecules
February 2015
Nuclear Pore Complex: Integrative Approach to Probe Nup133
February 2015
Piecing Together the Nuclear Pore Complex
February 2015
Updating ModBase
January 2015
Transmembrane Spans
December 2014
Mining Protein Dynamics
May 2014
Novel Proteins and Networks: Assigning Function
May 2014
Cancer Networks: Predicting Catalytic Residues from 3D Protein Structures
November 2013
The Immune System: A Brotherhood of Immunoglobulins
June 2013
The Immune System: Super Cytokines
June 2013
Infectious Diseases: Targeting Meningitis
May 2013
PDZ Domains
April 2013
Protein Interaction Networks: Adding Structure to Protein Networks
April 2013
Design and Discovery: Flexible Backbone Protein Redesign
February 2013
Pocket changes
July 2012
Predictive protein origami
July 2012
Refining protein structure prediction
March 2012
Metal mates
February 2012
Devil is in the details
January 2012
Playing while you work
November 2011
Docking and rolling
October 2011
Fit to serve
October 2011
Rosetta hone
July 2011
Structure from sequence
July 2011
An easier solution for symmetry
June 2011
Solutions in the solution
June 2011
Regulating nitrogen assimilation
January 2011
Guard cells pick up the SLAC
December 2010
Alpha/Beta Barrels
October 2010
Modeling RNA structures
May 2010
Deducing function from small structural clues
February 2010
Spot the pore
January 2010
Network coverage
November 2009
GPCR modeling: any good?
August 2009
Protein modeling made easy
July 2009
Model proteins in your lunch break
April 2009
Click for cancer-protein interactions
December 2008
Modeling with SAXS
October 2008
Designing activity
September 2008

Technology Topics Modeling

Solutions in the solution

SBKB [doi:10.1038/sbkb.2011.24]
Technical Highlight - June 2011
Short description: A high-throughput analysis demonstrates the complementary power of SAXS with other structural techniques.

Comparing of SAXS envelopes (gray) with NMR (left) and X-ray crystallographic (right) structuraldata shows that SAXS is a powerful complementary technique for other structural approaches. Image by Edward Snell and Thomas Grant.

Small-angle X-ray scattering (SAXS) relies on X-ray radiation to generate structural information of proteins in solution. While it can't provide the atomic-level detail that X-ray crystallography provides, it has the advantage of not requiring crystallization of the target protein. This is of great importance, as most proteins targeted to date have not been successfully crystallized. Alternatively, NMR spectroscopy can also provide structural information for proteins that cannot be crystallized, but this technique has limitations, in particular, time constraints and the size of the protein being examined. Thus, SAXS has for some time provided a valid option for proteins that are not easily examined by either NMR spectroscopy or X-ray crystallography. It can also be used to provide additional data for structure refinement, particularly of protein NMR structures.

One distinct advantage of SAXS is its ability to be used in a high-throughput approach, owing to the relatively simple sample preparation required and its rapid data collection. Now, Snell and colleagues (Hauptman-Woodward Medical Research Institute and PSI NESG) have carried out a high-throughput analysis of proteins whose X-ray crystal and/or NMR structures have been determined, demonstrating that SAXS can function as a complementary technique for other structural analyses.

When compared to X-ray crystallography data, SAXS ab initio envelopes generally gave similar values to the radius of gyration (R g) and maximum particle dimension (D max) calculated from the crystal data. Places where the SAXS envelope extended beyond the crystal structure were easily explained by side chains and areas where the crystal structure is disordered, thus providing information that was not available from the crystal structure alone. Similarly, R g and D max values were also in good agreement between SAXS and NMR data, although SAXS D max values tended to be smaller. Occasional discrepancies between the two methods were usually caused by disordered and dynamic residues, as the SAXS envelopes were much less sensitive to extreme changes in protein conformations.

An area for caution was found in the analysis of solutions of mixed oligomers and monomers. Although the authors were able to significantly improve the fit of the data by compensating for a mixture of monomers, dimers and/or tetramers for the proteins examined, they note that this is possible only with knowledge of the protein structure. They caution that ab initio reconstructions should not be used in situations in which the solution is likely to be a mix of oligomers.

Although SAXS lacks the resolution that NMR and X-ray crystallography offer, the ability to use it on virtually any soluble, purified sample makes it a powerful technique for structural analysis. And for those situations in which other structural data is also available, it can greatly enhance our understanding of protein structure in vivo.

Steve Mason


  1. T. Grant et al. Small angle x-ray scattering as a complementary tool for high-throughput structural studies.
    Biopolymers (1 April 2011). doi:10.1002/bip.21630

Structural Biology Knowledgebase ISSN: 1758-1338
Funded by a grant from the National Institute of General Medical Sciences of the National Institutes of Health