The cryo-electron-microscopy resolution revolution in structural biology.

Structural biology has been a major driver of progress in biological research over the past four decades. Up to 2015 such progress has been based on X-ray crystallography (thanks to synchrotron sources) and on NMR. Following two main technical developments (cryo-protection of the samples and availability of electron-counting detectors), from 2015 on single particle cryo-electron-microscopy (cryoEM) has been providing 3D structures of biological macromolecules at near-atomic resolution (often well below 3.0 A). The cryoEM approach to the structure of biological matter meets important criteria. On the one hand, it provides 3D structures of macromolecules in (vitrified) solution. On the other hand, it requires tiny amounts (0.1 mg) of material. In addition, the approach can be fast (days), and large molecular assemblies can be reliably handled, even if not highly purified. The size of the structural data bank (EMBD) associated to such approaches is growing exponentially. Importantly, the structural organization of specific biological specimens (to be presented), such as amyloid protein fibrils, can be approached only through cryoEM.