High Resolution Distance Distributions Determined by X-Ray and Neutron Scattering
Measuring distances within or between macromolecules is necessary to understand the chemistry that biological systems uniquely enable. In performing their chemistry, biological macromolecules undergo structural changes over distances ranging from atomic to micrometer scales. X-ray and neutron scattering provide three key assets for tackling this challenge. First, they may be conducted on solutions where the macromolecules are free to sample the conformations that enable their chemistry. Second, there are few limitations on chemical environment for experiments. Third, the techniques can inform upon a wide range of distances at once. Thus scattering, particularly recorded at small angles (SAS), has been applied to a large variety of phenomenon. A challenge in interpreting scattering data is that the desired three dimensional distance information is averaged onto one dimension. Furthermore, the scales and variety of phenomenon interrogated have led to an assortment of functions that describe distances and changes thereof. Here we review scattering studies that characterize biological phenomenon at distances ranging from atomic to 50 nm. We also distinguish the distance distribution functions that are commonly used to describe results from these systems. With available X-ray and neutron scattering facilities, bringing the action that occurs at the atomic to the micrometer scale is now reasonably accessible. Notably, the combined distance and dynamic information recorded by SAS is frequently key to connecting structure to biological activity and to improve macromolecular design strategies and outcomes. We anticipate widespread utilization particularly in macromolecular engineering and time-resolved studies where many contrasting experiments are necessary for resolving chemical mechanisms through structural changes.
KeywordsSAXS Pair distribution Pair correlation Protein structure Resolution Molecular ruler
- Baldock C, Oberhauser AF, Ma L, Lammie D, Siegler V, Mithieux SM, Tu Y, Chow JY, Suleman F, Malfois M, Rogers S, Guo L, Irving TC, Wess TJ, Weiss AS (2011) Shape of tropoelastin, the highly extensible protein that controls human tissue elasticity. P Natl Acad Sci USA 108:4322–4327CrossRefGoogle Scholar
- Horkay F, Hecht AM, Rochas C, Basser PJ, Geissler E (2006) Anomalous small angle x-ray scattering determination of ion distribution around a polyelectrolyte biopolymer in salt solution. J Chem Phys 125Google Scholar
- Hura GL, Menon AL, Hammel M, Rambo RP, Poole FL II, Tsutakawa SE, Jenney FE Jr, Classen S, Frankel KA, Hopkins RC, Yang S-J, Scott JW, Dillard BD, Adams MWW, Tainer JA (2009) Robust, high-throughput solution structural analyses by small angle X-ray scattering (SAXS). Nat Methods 6:606–U683CrossRefPubMedPubMedCentralGoogle Scholar
- Hura GL, Tsai CL, Claridge SA, Mendillo ML, Smith JM, Williams GJ, Mastroianni AJ, Alivisatos AP, Putnam CD, Kolodner RD, Tainer JA (2013b) DNA conformations in mismatch repair probed in solution by X-ray scattering from gold nanocrystals. Proc Natl Acad Sci U S A 110:17308–17313CrossRefPubMedPubMedCentralGoogle Scholar
- Mathew-Fenn RS, Das R, Silverman JA, Walker PA, Harbury PAB (2008a) A molecular ruler for measuring quantitative distance distributions. PLoS One 3Google Scholar