Low-Resolution Structure of Detergent-Solubilized Membrane Proteins from Small-Angle Scattering Data.

Despite the ever-increasing usage of small-angle scattering as a valuable complementary method in the field of structural biology, applications concerning membrane proteins remain elusive mainly due to experimental challenges and the relative lack of theoretical tools for the treatment of scattering data. This fact adds up to general difficulties encountered also by other established methods (crystallography, NMR) for the study of membrane proteins. Following the general paradigm of ab initio methods for low-resolution restoration of soluble protein structure from small-angle scattering data, we construct a general multiphase model with a set of physical constraints, which, together with an appropriate minimization procedure, gives direct structural information concerning the different components (protein, detergent molecules) of detergent-solubilized membrane protein complexes. Assessment of the method's precision and robustness is evaluated by performing shape restorations from simulated data of a tetrameric α-helical membrane channel (Aquaporin-0) solubilized by n-Dodecyl β-D-Maltoside and from previously published small-angle neutron scattering experimental data of the filamentous hemagglutinin adhesin β-barrel protein transporter solubilized by n-Octyl β-D-glucopyranoside. It is shown that the acquisition of small-angle neutron scattering data at two different solvent contrasts, together with an estimation of detergent aggregation number around the protein, permits the reliable reconstruction of the shape of membrane proteins without the need for any prior structural information.