James Conway

The structure and function of macromolecular complexes, such as virus capsids, is accessible to cryo-electron microscopy for detailing protein folds and interfaces that determine function. Particular systems being studied include herpesviruses and dsDNA bacteriophages such as HK97, D3, T5 and others, These tailed phages have important structural similarities with each other and with herpesvirus, indicating a long evolutionary connection between them. The dynamic aspects of the virus lifecycle – assembly, DNA packaging, infection and DNA delivery – are often better suited to cryoEM study than crystallography. The recent technological advances in cryoEM allow the symmetry-breaking portal vertex of these capsids to be studied in detail, as well as the entire tail and tail-tip complexes. Further developments in modeling, including AlphaFold and Model Angelo, allow rapid fitting of protein sequences into density maps to reveal the complete organization of the capsid assembly machinery and the host recognition and infection complexes. Ultimately, we aim to characterize the structural and functional repertoire of a virus throughout its lifecycle, which will have benefits in understanding protein-protein and protein-DNA interactions as well as the evolution of protein structure, and in developing new targets for interfering with viral infection and replication, and technological application of the knowledge.