Biological macromolecules adopt complicated three-dimensional (3D) structures that are critical to their function. We want to learn how these complicated structures help macromolecules perform particular tasks. To do this we use a visualization technique called electron cryomicroscopy (cryo-EM), which involves firing a beam of high-energy electrons at a biological sample at cryogenic temperatures. Some of these electrons interact with the sample and when recorded form a 2D image of the sample. A 3D density map can then be formed from a series of these 2D images. In recent years the quality of these maps has improved rapidly and often have sufficient detail (resolution) to build an atomic model of the structure. This “resolution revolution” is the result of better microscopes, advances in electron detection, and new mathematical models for interpreting the raw images.
Cryo-EM has made the impossible possible. We can now visualize macromolecules that are structurally heterogeneous, produced at low yield, and, perhaps most excitingly, directly in their native environment.