Class of 2005
jeseedorff@jhu.edu

Research
Allosteric regulation is commonly used by regulatory proteins to alter gene expression in response to a stimuli. In allosteric regulation, an effector molecule binds to the regulatory protein, and this binding event alters the protein's ability to bind to DNA. The effector binding site and DNA binding site typically are in different domains, so understanding how the binding of an effector molecule is communicated to the DNA binding domain is essential to understanding the molecular basis for this type of gene regulation.

One example of an allosterically regulated regulatory protein is the Tetracycline Repressor (TetR). TetR is allosterically regulated by the antibiotic tetracycline. TetR prevents the expression of an antiporter, TetA, that provides a selective advantage for bacteria in the presence of tetracycline. However, in the absence of the antibiotic, expression of TetA is detrimental to cell survival, so TetR binds to DNA in order to prevent the expression of TetA. When tetracycline binds to TetR, a conformational change occurs which results in TetR releasing DNA. When the DNA is released, the promoter for TetA is exposed and TetA can be expressed. Using binding assays and previously published crystal structures, I am trying to understand on a molecular level how binding of tetracycline is able to modulate the DNA binding ability of TetR.

Publications
Knappenberger, J.A., J.E. Smith, S.H. Thorpe, J.A. Zitzewitz, and C.R. Matthews. (2002) A buried polar residue in the hydrophobic interface of the coiled-coil peptide, GCN4-p1, plays a thermodynamic, not a kinetic role in folding. J. Mol. Bio. 321:1-6.