Near-atomic resolution cryo-EM for molecular virology

Electron cryo-microscopy (cryo-EM) is a technique in structural biology that is widely used to solve the three-dimensional structures of macromolecular assemblies, close to their biological and solution conditions. Recent improvements in cryo-EM and single-particle reconstruction methodologies have led to the determination of several virus structures at near-atomic resolution (3.3–4.6 Å). These cryo-EM structures not only resolve the Cα backbones and side-chain densities of viral capsid proteins, but also suggest functional roles that the protein domains and some key amino acid residues play. This paper reviews the recent advances in near-atomic-resolution cryo-EM for probing the mechanisms of virus assembly and morphogenesis.

► Cryo-EM resolves structures of viruses in native state with fine detail and high fidelity. ► Cryo-EM uncovers protein folds of virus capsid shells. ► Cryo-EM correlates structure and function of protein domains and key amino acid residues. ► Cryo-EM resolves structures of regions which cannot be seen in X-ray crystallography. ► Cryo-EM detects tertiary structural changes of capsid shells during virus morphogenesis.