High-resolution icosahedral reconstruction: fulfilling the promise of cryo-electron microscopy

Two recent papers have defined the secondary structure of the hepatitis B virus capsid using a combination of cryoelectron microscopy and icosahedral image reconstruction. These two papers do more than reveal a new fold for a virus protein; they herald a new era in which image reconstruction of single particles will provide reliable high-resolution structural information. In revealing the promise of these techniques to the structural biology community, their two papers should play a seminal role for single particle work, similar to that of the work of Unwin and Henderson [I] on bacteriorhodopsin in revealing the potential of electron microscopy of membrane protein crystals. Indeed, the success of these single particle methods owes much to the development of high-resolution techniques for two-dimensional crystals. This review will summarize some of the history of icosahedral reconstruction from cryo-electron micrographs, compare the two different approaches used to obtain the recent results and outline some of the challenges and promises for the future.