Combining X-ray crystallography and electron microscopy

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.