The combination of cryo-electron microscopy to study large biological assemblies at low resolution with crystallography to determine near atomic structures of assembly fragments is quickly expanding the horizon of structural biology. This technique can be used to advantage in the study of large structures that cannot be crystallized, to follow dynamic processes, and to "purify" samples by visual selection of particles. Factors affecting the quality of cryo-electron microscopy maps and limits of accuracy in fitting known structural fragments are discussed.
Bibliographical noteFunding Information:
The structural examples given here are derived from a large number of collaborators, postdoctoral researchers, graduate students, and technical assistants who are recognized by virtue of the quoted references. Similarly, the sources of financial support are numerous, but successive National Institutes of Health grants have supported work on the eukaryotic viruses, while successive National Science Foundation grants and a Human Frontier Science Program grant have supported the bacteriophage studies. We thank Cheryl Towell for her help in preparing this manuscript.