One cryo-ET tag to solve them all

To understand the functions of proteins, it is important to understand their three-dimensional structures. This has been done for many years on purified macromolecules ex situ using X-ray crystallography, NMR and single-particle analysis electron microscopy. Recently it has become possible to obtain structures of single proteins in situ using cryo-electron tomography (cryo-ET), enabling the investigation of proteins located in their natural environment within cells. The proteins possible to identify so far are highly abundant and large in size, but as only very few proteins fall into the category the biological output of cryo-ET is still limited. For the field to move forward it needs the opportunity to identify rare and smaller proteins in cryo-ET. To do so, a universal tag that provide both recognizability, size and rigidity to help identify and solve the structure of the protein of interest is needed.