Article

Small-angle neutron scattering and contrast variation: A powerful combination for studying biological structures

Center for Structural Molecular Biology and Chemical Sciences Division, Oak Ridge National Laboratory, PO Box 2008, MS-6393, Oak Ridge, TN 37831, USA.
Acta Crystallographica Section D Biological Crystallography (Impact Factor: 2.67). 11/2010; 66(Pt 11):1213-7. DOI: 10.1107/S0907444910017658
Source: PubMed

ABSTRACT

The use of small-angle scattering (SAS) in the biological sciences continues to increase, driven as much by the need to study increasingly complex systems that are often resistant to crystallization or are too large for NMR as by the availability of user facilities and advancements in the modelling of biological structures from SAS data. SAS, whether with neutrons (SANS) or X-rays (SAXS), is a structural probe of length scales ranging from 10 to 10,000 Å. When applied to biological complexes in dilute solution, it provides size and shape information that can be used to produce structural models that can provide insight into function. SANS enables the use of contrast-variation methods through the unique interaction of neutrons with hydrogen and its isotope deuterium. SANS with contrast variation enables the visualization of components within multisubunit complexes, making it a powerful tool for probing protein-protein and protein-nucleic acid complexes, as well as the interaction of proteins with lipids and detergents.

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    • "One recent study used SANS to characterize the regular spacing of molecules within droplets comprised of the nucleolar protein, nucleophosmin (NPM1), and a peptide derived from the ribosomal protein, rpL5, on length scales from 5.5 to 11.9 nm [NPM1 integrates within the nucleolus via multi-modal interactions with proteins displaying R-rich linear motifs and rRNA: Mitrea DM, et al., under review]. SANS has the advantage of allowing detection of scattering from specific components within heterogenous, phase separated states through selective protonation and/or deuteration and solvent contrast matching[93]. Furthermore, time-resolved SANS has been used in the past in studies of mutant huntingtin exon 1 phase separation into amyloid fibers to determine the mechanism of macromolecular assembly and the geometry of monomer packing within the fibrils[94]. "
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