Emerging applications of small angle solution scattering in structural biology

Abstract

Small angle solution X-ray and neutron scattering recently resurfaced as powerful tools to address an array of biological problems including folding, intrinsic disorder, conformational transitions, macromolecular crowding, and self or hetero-assembling of biomacromolecules. In addition, small angle solution scattering complements crystallography, nuclear magnetic resonance spectroscopy, and other structural methods to aid in the structure determinations of multidomain or multicomponent proteins or nucleoprotein assemblies. Neutron scattering with hydrogen/deuterium contrast variation, or X-ray scattering with sucrose contrast variation to a certain extent, is a convenient tool for characterizing the organizations of two-component systems such as a nucleoprotein or a lipid-protein assembly. Time-resolved small and wide-angle solution scattering to study biological processes in real time, and the use of localized heavy-atom labeling and anomalous solution scattering for applications as FRET-like molecular rulers, are amongst promising newer developments. Despite the challenges in data analysis and interpretation, these X-ray/neutron solution scattering based approaches hold great promise for understanding a wide variety of complex processes prevalent in the biological milieu.

Using Small-Angle Scattering and Contrast Matching to Understand Molecular Packing in Low Molecular Weight Gels

“…Here, we focus on this question and apply microscopic and small-angle scattering approaches. We combine small-angle X-ray scattering (SAXS) with small-angle neutron scattering (SANS) contrast-matching experiments to access information about the molecular packing; this approach is widely used in the surfactant literature [42][43][44][45] as well as (for example) structure determination in protein and polymer systems. [46][47][48][49] We start by describing a single well-studied and robust LMWG, 2NapFF ( Figure 1).…”

Apurinic/apyrimidinic (AP) endonuclease 1 processing of AP sites with 5′ mismatches

“…Unfortunately, the exact location of H atoms, and therefore hydrogen bonds, cannot easily be determined using X-ray crystallography. The implementation of neutron crystallography would allow the accurate modeling of H atoms, and consequently elucidation of the unknown protonation states (Chaudhuri, 2015;Ho et al, 2004;Moon et al, 2016). Through the presentation of this study at the International Symposium on Diffraction Structural Biology 2016, we intended to shine light on the specific challenges associated with elucidating base-pairing properties, and assigning hydrogen-bonding interactions in general, based on the implied protonation states and X-ray crystallographic data alone.…”

Structure and function analysis of protein–nucleic acid complexes

“…The improved approach to mathematical methods for processing and analyzing smallangle scattering data for proteins, nucleic acids and protein ± nucleic acid complexes, which takes into account the scattering contribution from excess electron density around the surface of the protein ± NA complex, was proposed by Ravikumar et al 103 Emerging applications of small-angle scattering techniques in structural biology were considered by Chaudhuri. 104 The improvement of experimental methods and considerable progress in computer modelling and methods for mathematical processing of experimental data led to a rapid increase in the amount of experimental small-angle scattering data and the growing number of publications. This generates a need for a global repository in order to compile, systematize and store small-angle scattering data.…”