Lawrence Reitzer, Ph.D.
Education and Professional Affiliations
B.S., Biology, Case Western Reserve University
Ph.D., Molecular and Cell Biology, Washington University
Postdoctoral work, Fellow at the Massachusetts Institute of Technology
Member, Undergraduate Education Committee.
Dr. Reitzer’s research involves the regulation of gene expression and metabolism in Escherichia coli and pathogenic bacteria with a focus on responses to environmental stresses, such as nitrogen limitation. Work in progress is also analyzing pathways of the catabolism of polyamines, compounds which correlate with growth rate, and the function of transaminases, especially with respect to the function of their broad specificity.
The response regulator NtrC transcriptionally activates genes of the nitrogen-regulated (Ntr) response. Phosphorylation of its N-terminal receiver domain stimulates an essential oligomerization of the central domain. Deletion of the central domain reduces, but does not eliminate, intermolecular interactions as assessed by cooperative binding to DNA. To analyze the structural determinants and function of this central domain-independent as well as phosphorylation-independent oligomerization, we randomly mutagenized DNA coding for an NtrC without its central domain and isolated strains containing NtrC with defective phosphorylation-independent cooperative binding. The alterations were primarily localized to helix B of the C-terminal domain. Site-specific mutagenesis that altered surface residues of helix B confirmed this localization. The purified NtrC variants, with or without the central domain, were specifically defective in phosphorylation-independent cooperative DNA binding and had little defect, if any, on other functions, such as non-cooperative DNA binding. We propose that this region forms an oligomerization interface. Full-length NtrC variants did not efficiently repress the glnA-ntrBC operon when NtrC was not phosphorylated, which suggests that phosphorylation-independent cooperative binding sets the basal level for glutamine synthetase and the regulators of the Ntr response. The NtrC variants in these cells generally, but not always, supported wild-type growth in nitrogen-limited media and wild-type activation of a variety of Ntr genes. We discuss the differences and similarities between the NtrC C-terminal domain and the homologous Fis, which is also capable of intermolecular interactions.
1. Reitzer, L. 2003. Nitrogen Assimilation and Global Regulation in Escherichia Coli. Annu. Rev. Microbiol. 57:155-176
2. Harrod, C.A., S. Yang, M. Junker and L. Reitzer. 2003. Evidence for a Second Interaction between the Regulatory Amino-terminal and Central Output Domains of the Response Regulator NtrC (Nitrogen Regulator I) in Escherichia coli. The Journal of Biological Chemistry. 279:2350-2359.
3. Chaussee, M.S., G.A. Somerville, L. Reitzer and J.M. Musser. 2003. Rgg Coordiantes Virulence Factor Synthesis and Metabolism in Streptococcus pyogenes. Journal of Bacteriology. 185:6016-6024.
4. Yang, X.F., J. Youngran, B.L. Schneider and L. Reitzer. 2004. Phosphorylation-independent Dimer-Dimer Interactions by the Enhancer-binding Activator NtrC of Escherichia coli. The Journal of Biological Chemistry. 279:36708-36714.
- Updated: February 6, 2006