Ribosomes and cryo-EM: a duet

Ribosomes and electron cryomicroscopy (cryo-EM) share a long, intertwined history. However, cryo-EM only recently usurped X-ray crystallography as the predominant structural method to study ribosomes in atomic detail. The main, but not only, reason for this succession was the introduction of direct-electron detectors enabling cryo-EM to achieve equally high resolutions. Here, we describe how cryo-EM sample preparation and data processing allows new types of structural analyses not possible by X-ray crystallography. Taking advantage of these approaches, cryo-EM structures have revealed unprecedented insights into the function of ribosomes from a wide range of biological sources and in numerous physiological contexts. These include the discovery of a new mechanism of polypeptide synthesis and the identification of the roles of ribosomes in functional supercomplexes.