Egan


	Susan Egan Associate Professor Department of Molecular Biosciences Division of Biological Sciences Protein-Protein Interactions Required for Transcription Activation by RhaR	Mentor: Mark Richter
Many activator proteins function by directly contacting RNA polymerase (RNAP), however the exact effects of these interactions are generally not understood. The long-range goal of this project is to elucidate the structure of the transcription activator protein RhaR and to relate this structure to the molecular mechanisms used by RhaR to activate transcription. In the presence of L-rhamnose, RhaR activates expression of the Escherichia coli rhaSR operon. Full activation of rhaSR expression also requires the CRP protein. The central hypothesis is that specific interactions between RhaR, CRP and RNAP are required for transcription activation. Structural information for RhaR will enable a more detailed understanding of these interactions. The aims of this research are to conduct a structural analysis of the RhaR protein; characterize RhaR interactions with RNAP, and characterize RhaR interactions with CRP. They will also test whether RhaR interacts with the RNAP alpha-subunit C-terminal domain, and if so, biochemically characterize these interactions. Egan will determine whether direct contacts between RhaR and CRP contribute to the apparent ability of RhaR to influence the DNA sites in the rhaSR promoter to which CRP binds. Egan's research group plans to use X-ray crystallography to determine the structure of RhaR.
		The other goal of the proposal is to characterize the interactions that RhaR makes with RNA polymerase (RNAP) and CRP, and to correlate this functional information with the structure. Egan will biochemically characterize two contacts between RhaR and the RNAP sigma70 subunit that her group has genetically identified. The findings that many regions of the crystal structures of a bacterial and a yeast RNAP can be virtually superimposed suggests that eukaryotic and prokaryotic RNAP may utilize similar mechanisms for interaction with activators.
Also, RhaR is a member of the large AraC/XylS family of activators (>800 members), many of which activate virulence factors in bacterial pathogens and are of interest as antibacterial targets. Understanding the mechanisms used by AraC/XylS family members to activate transcription will be important for rational design of anti-AraC/XylS family agents. Dr. Egan graduated from the COBRE program in 2005 when she was awarded an NIH R01 grant " Transcription Activation at the rhaBAD Operon."
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