Structures of viral membrane proteins by high-resolution cryoEM.

Cryo electron microscopy (cryoEM) has emerged as an excellent tool for resolving high-resolution three-dimensional structures of membrane proteins in a lipid-containing environment with interacting partners. The near atomic resolution structures of Venezuelan equine encephalitis virus and dengue virus revealed transmembrane helices in lipid bilayers, receptor-binding glycosylation moieties, and functionally important interactions between their fusion protein and membrane-anchored chaperone protein. For pleomorphic enveloped viruses, such as human immunodeficiency virus, glycoprotein complexes can be imaged in isolation to reveal molecular interactions at different states. These high-resolution cryoEM structures have clarified important domains not previously resolved by crystallography and illustrate exciting opportunities to visualize viral membrane proteins in their native and possibly transiently stable functional states, thus uncovering mechanisms of action and informing anti-viral strategies.