Refining structural models of membrane proteins with disordered domains in phospholipid nanodiscs

Small-angle scattering can be used to derive structural information about membrane proteins reconstituted in suitable carrier systems enabling solubilization of the membrane proteins in question. Since the studies are done in solution, there is no need for crystallization or deposition on sample grids, and it is in principle possible to obtain structural information about intrinsically disordered regions which cannot be resolved by crystallography or the quantitative link to which is hard to establish using e.g. electron microscopy methods. In this study, tetramers of the gated spinach aquaporin SoPIP2;1 were reconstituted into nanodiscs and small-angle x-ray scattering data were recorded. From these data, we refine structural models of the entire nanodisc-membrane protein complex including the flexible regions using newly developed models based on Fast Debye sums. We introduce software for these computations available via online repositories and discuss the implications and limitations of these methods. ### Competing Interest Statement The authors have declared no competing interest.