Cryo Electron Microscopy: the resolution revolution
The past two years have witnessed a revolution in structural biology single-particle cryo-EM has begun to reach the atomic resolutions formerly only available through crystallography where chemistry can be related to both structure and sequence. Importantly, however, cryo-EM does not require the formation of crystals and only minuscule amounts of homogeneous sample are necessary. In principle any biological problem is within reach, and sample preparation is the primary if not only limiting factor. There is a second revolution brought about by electron microscopy. Electron cryo-tomography (cryo-ET) now offers the possibility of studying cellular structures in both physiological and pathological conditions at an unprecedented level of detail. A useful and increasingly utilized approach is to image the same structures with both cryo-ET and fluorescence microscopy. Indeed, the rapidly expanding power of fluorescence microscopy is ideally suited to identify areas and events of interest within cells, which are then examined in molecular detail by electron imaging via cryo-ET.