Simultaneous Determination of Protein Structure and Dynamics Using Cryo-Electron Microscopy

Cryo-electron microscopy is rapidly emerging as a powerful technique to determine the structures of complex macromolecular systems elusive to other techniques. Since many of these systems are highly dynamical, characterising also their movements is a crucial step to unravel their biological functions. To achieve this goal, we report an integrative modelling approach to simultaneously determine structure and dynamics from cryo-electron microscopy density maps. By quantifying the level of noise in the data and dealing with their ensemble-averaged nature, this approach enables the integration of multiple sources of information to model ensembles of structures and infer their populations. We illustrate the method by characterising structure and dynamics of the integral membrane receptor STRA6, thus providing insights into the mechanisms by which it interacts with retinol binding protein and translocates retinol across the membrane.