Transcription initiation, the first step in gene expression, is the step at which most regulation of gene expression occurs. Richard Ebright's lab seeks to understand the structure, function, and regulation of transcription initiation complexes and to develop gene-specific inhibitors of transcription initiation as potential therapeutic agents.
Illustration description: Crystallographic structure of a transcriptional activator (catabolite activator protein, CAP; cyan) in complex with its target in the transcriptional machinery (RNA polymerase a-subunit C-terminal domain, aCTD; green) and DNA (red). There are no large-scale conformational changes in the activator and target, and the interface between the activator and target is small (residues highlighted in navy and yellow) consistent with the proposal that transcriptional activation involves a simple "recruitment" mechanism.
See Benoff, B., Yang, H., Lawson, C.L., Parkinson, G., Liu, J., Blatter, E., Ebright, Y.W., Berman, H.M., and Ebright, R.H. 2002. Science 297:1562-1566.
Year of Research Highlight: 2002