Helical reconstruction, again

Many protein and nucleoprotein complexes exist as helical polymers. As a result, much effort has been invested in developing methods for using electron microscopy to determine the structure of these assemblies. With the revolution in cryo-electron microscopy (cryo-EM), it has now become routine to reach a near-atomic level of resolution for these structures, and it is the exception when this is not possible. However, the greatest challenge is frequently determining the correct symmetry. This review focuses on why this can be so difficult and the current absence of a better approach than trial-and-error.