Direct extraction of active membrane proteins and complexes for cryo-EM

The resolution revolution in cryogenic electron microscopy (cryo-EM) has paved the way to highresolution structures of challenging membrane proteins. However, sample preparation remains a bottleneck as most membrane proteins lose their native activity and/or become unstable when removed from biological cell membranes. Indeed, extraction of challenging membrane proteins in their active state is by all means the holy grail in the field of membrane protein structural biology. Here, the aim is to develop a system capable of extracting membrane proteins directly from cell membranes into small particles suitable for cryo-EM. The extracted particles will retain the biophysical properties and the biomolecular composition of the cell membrane and will have superior stability to currently available agents. This technology will facilitate studies of hitherto inaccessible membrane proteins, which is crucial for advancing our understanding of this important class of proteins.