Our research focuses on the structure and mechanism of viral replication and infection machinery using X-ray crystallography and cryo-electron microscopy. High-resolution X-ray crystal structures of individual component proteins can be fitted into lower resolution cryo-EM density maps to generate pseudo-atomic structure of large macromolecular complexes.
Crystal structure of BVDV polymerase. The N-terminal, fingers, palm, and the thumb domain are shown in yellow, blue, green, and red, respectively.
|Structure of bacteriophage N4 determined by cryo-EM and 3D image reconstruction techniques.|
Virtually all RNA viruses carry out viral genome replication using a large replication complex composed of RNA, viral replicases, and cellular proteins. However, specific protein-protein and protein-RNA interactions are poorly understood. We are interested in the structure of individual replication enzymes and their protein-protein, and protein-RNA complexes in human and animal viruses. These viruses include hepatitis C virus, bovine viral diarrhea virus (BVDV), dengue virus, human coronavirus (SARS), and hantan virus. Our structural studies will help develop antiviral therapeutics for animal and human diseases caused by these RNA viruses.
Tailed bacteriophages have to deliver their genetic information into the host cell's cytoplasm across cell membranes. The tail machinery, composed of multiple protein components, attaches to the cell membrane and transports genomic DNA into the cell. We use bacteriophage N4 as a model system to study the mechanism of genome and protein transport from the virus into the host cell. N4 packages dsDNA as well as one or two copies of a 3,500-amino acid RNA polymerase (vRNAP) inside the capsid, which is then ejected into host cell upon infection. In collaboration with Dr. Lucia Rothman-Denes laboratory (University of Chicago), we are determining the structure of N4 virions as well as tail component proteins.