Transcription is a complex, multi-step process.
Each step in this elaborate reaction involves changes in the conformation of the RNA polymerase and in the configuration of the DNA and RNA within the transcription complex. We are using T7 RNA polymerase as a model system to explore the conformational dynamics of transcription. Through a combination of directed mutagenesis, crystallography, structure-based molecular modeling, kinetic analysis, and the use of enzymatic and chemical probes to monitor changes in protein and nucleic acid interactions and conformation, we are generating a detailed and realistic movie of how an RNA polymerases progresses through a transcription reaction. A second interest of the lab is in elucidating the structures of proteins which interact with clathrin to assemble and disassemble clathrin cages. Such cages mediate much of the vesicle trafficking in eukaryotic cells, and their assembly and disassembly are regulated processes which represents important points of control in cellular physiology.