Two lines of study, one dealing with factors that initiate higher plant cell division and the other involving pathogenesis in a prokaryotic pathogen of this plant, have intersected at a single xenognostic growth factor involved in the control of both events. Structural analysis of the growth factor has led to a mechanistic model for the activation event. This model has provided valuable insight and enabled the development of both reversible and irreversible specific inhibitors of Agrobacterium tumefaciens virulence gene expression. By exploiting the inhibitors and the molecular genetics of the pathogen, specific receptor proteins, Xpb proteins, have been identified. The outlined experiments will (i) isolate and characterize the Xpa proteins, (ii) characterize the mechanism by which the growth factor-Xpb complex activates a two-component phosphorylation cascade controlling virulence gene expression, (iii) select and characterize mutants that alter sensitivity to the growth factor, and (iv) analyze specific mutants of the autokinase involved in the signal transduction. Successful completion of the proposed experiments will significantly expand our understanding of phenolic perception of prokaryotes, providing at least a model, if not the proteins for eukaryotic perception, as well as provide the first insight into how two-component regulatory systems recognize and transduce signal output. Related growth factors serve critical roles in animal and plant systems and the opportunity to study the mechanism of these factors in the context of pathogenesis is unique. The knowledge gained will provide insight into the control of eukaryotic cell division as well as define strategies involved in pathogenesis. Two laboratories have combined their expertise in order to exploit the chemical, biochemical and molecular genetic approaches necessary for the efficient execution of these experiments.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM047369-07
Application #
6018888
Study Section
Special Emphasis Panel (ZRG3-BNP (02))
Project Start
1992-04-01
Project End
2000-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
7
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Chicago
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
Nair, Gauri R; Lai, Xiaoqin; Wise, Arlene A et al. (2011) The integrity of the periplasmic domain of the VirA sensor kinase is critical for optimal coordination of the virulence signal response in Agrobacterium tumefaciens. J Bacteriol 193:1436-48
Wise, Arlene A; Fang, Fang; Lin, Yi-Han et al. (2010) The receiver domain of hybrid histidine kinase VirA: an enhancing factor for vir gene expression in Agrobacterium tumefaciens. J Bacteriol 192:1534-42
He, Fanglian; Nair, Gauri R; Soto, Cinque S et al. (2009) Molecular basis of ChvE function in sugar binding, sugar utilization, and virulence in Agrobacterium tumefaciens. J Bacteriol 191:5802-13
Gao, Rong; Lynn, David G (2007) Integration of rotation and piston motions in coiled-coil signal transduction. J Bacteriol 189:6048-56
Yuan, Ze-Chun; Edlind, Merritt P; Liu, Pu et al. (2007) The plant signal salicylic acid shuts down expression of the vir regulon and activates quormone-quenching genes in Agrobacterium. Proc Natl Acad Sci U S A 104:11790-5
Maresh, Justin; Zhang, Jin; Tzeng, Yih-Ling et al. (2007) Rational design of inhibitors of VirA-VirG two-component signal transduction. Bioorg Med Chem Lett 17:3281-6
Wise, Arlene A; Liu, Zhenying; Binns, Andrew N (2006) Three methods for the introduction of foreign DNA into Agrobacterium. Methods Mol Biol 343:43-53
Maresh, Justin; Zhang, Jin; Lynn, David G (2006) The innate immunity of maize and the dynamic chemical strategies regulating two-component signal transduction in Agrobacterium tumefaciens. ACS Chem Biol 1:165-75
Wise, Arlene A; Liu, Zhenying; Binns, Andrew N (2006) Nucleic acid extraction from Agrobacterium strains. Methods Mol Biol 343:67-76
Wise, Arlene A; Liu, Zhenying; Binns, Andrew N (2006) Culture and maintenance of Agrobacterium strains. Methods Mol Biol 343:3-13

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