Biological Small Angle Scattering: Techniques, Strategies and Tips

Frank Gabel

Small angle neutron scattering (SANS) is a powerful tool to obtain structural information on solubilized membrane proteins on the nanometer length-scale in complement to other structural biology techniques such as cryo-EM, NMR and SAXS. In combination with deuteration of components and/or contrast variation (H2O:D2O exchange in the buffer) SANS allows to separate structural information from the protein and the detergent/lipid parts in solution. After a short historical overview on results obtained by SANS on membrane protein systems, this book chapter introduces the basic theoretical principles of the technique as well as requirements on samples. The two introductory sections are followed by an illustration of the specific consequences of sample heterogeneity of solubilized membrane proteins in the presence of detergent/lipid molecules on the interpretation of structural information by using simple, geometric models. The next sections deal with more sophisticated modelling approaches including ab initio shape reconstructions and full-atomic models in the presence of detergent/lipid and specific results obtained by these approaches. After a short comparison with the SAXS technique, this book chapter concludes with an overview of present and future developments and impact that can be expected by SANS on membrane structural biology in the coming years.