Multi-disciplinary studies of viruses: The role of structure in shaping the questions and answers

This contribution to the 50th anniversary issue of the Journal of Structural Biology traces a path in which the author evolved from seeing macromolecular structure as end in it self to a means of organizing and correlating data from many sources. The author looks at where we have been and where we are going in this enterprise and the role that structure plays in defining ever more ambitious biological questions and testing and refining models that incorporate data from many techniques. In this, essentially, personal account, the author reflects on 35 years of structural virology and the stages experienced; from “stand alone” crystallography of virus particles to the study of virus assembly and maturation in vitro and eventually into the entire virus infection process from particle cell entry to egress. In the process data from many sources were incorporated into reasonable and testable models based on structures ranging in resolution from near-atomic determined by crystallography, to nanometer, determined by electron cryo-microscopy and image reconstruction, to five nanometer tomographic studies in the cell. The technological development over this period, for structural studies at all resolutions and functional studies that were unimaginable three decades ago, has been astonishing. Here we look at an aspect of this development applied to virology.