Complementing crystallography: the role of cryo-electron microscopy in structural biology

Dramatic improvements in experimental methods and computational techniques have revolutionized three-dimensional image reconstruction from electron mi crographs (EM) of vitrified samples. Recent results include the first deter mination of a protein fold (for the core protein of the hepatitis B virus) by non-crystalline imaging techniques. These developments have generated in terest within the crystallographic community and have led to a re-evaluatio n of the technique, particularly amongst those working in the field of viru s structure or struggling with the phasing of large macromolecular assembli es. A simple discussion of the techniques of EM image reconstruction and it s advantages and problems in terms familiar to crystallographers will hopef ully allow an appreciation of the essential complementarity of the two tech niques and the practical potentials for phasing applications.