The overall objective of our research is to understand how protein interactions determine subcellular structure. Structural studies of viruses have contributed significantly over the years to understanding the principles of protein assembly, as well as to elucidating the molecular basis of viral pathogenesis. We are following that effort with similar studies of the rotavirus internal capsid particle and with structural analyses of the reo- and rotavirus proteins that mediate receptor binding and penetration. A recently determined structure of the L1 protein from human papillomavirus shows important parallels with polyomavirus VP1 and a striking concentration of variability in the outward-facing surface loops.
Similar changes are probably general features of DNA polymerases.
Longer-range goals include even more elaborate assemblies. We have begun to analyze the structures of these proteins and the specificity of their interactions, in collaboration with groups at Harvard Medical School. We have also initiated a collaborative effort to study the structural basis of protein translocation across membranes.