Supplanting crystallography or supplementing microscopy? A combined approach to the study of an enveloped virus

The recent advances in the resolution obtained by single‐particle reconstructions from cryo‐electron microscopy (cryo‐­EM) have led to an increase in studies that combine X‐ray crystallographic results with those of electron microscopy (EM). Here, such a combination is described in the determination of the structure of an enveloped animal virus, Semliki Forest virus, at 9 Å resolution. The issues of model bias in determination of the structure, the definition of resolution in a single‐particle reconstruction, the effect of the correction of the contrast‐transfer function on the structure determined and the use of a high‐resolution structure of a subunit in the interpretation of the structure of the complex are addressed.