Signal transduction in bacteria is often mediated by two-component systems, which are used by bacteria to regulate important cellular processes. These systems utilize a conserved phosphotransfer mechanism in which a sensor histidine kinase protein transfers a phosphoryl group to the regulatory domain of a response regulator protein, which in turn regulates the biological activity in question. Response regulators are attractive targets for the development of antimicrobial drugs and a detailed understanding of their mechanism of regulation is needed. This proposal is aimed at assessing the generality of the mechanism by which response regulators function. It will focus on the relative contributions of intramolecular interactions between regulatory and effector domains vs. the intermolecular interactions of regulatory domains between dimers of response regulators. This will be done using the large OmpR/PhoB subfamily of transcription factors as a model. Studies will include the construction and characterization of response regulator chimeras as well as the full-length proteins and individual domains. In addition, structural characterization by X-ray crystallography of activated regulatory domains of OmpR/PhoB subfamily functional dimers will be pursued. ? ?
| Toro-Roman, Alejandro; Mack, Timothy R; Stock, Ann M (2005) Structural analysis and solution studies of the activated regulatory domain of the response regulator ArcA: a symmetric dimer mediated by the alpha4-beta5-alpha5 face. J Mol Biol 349:11-26 |
| Toro-Roman, Alejandro; Wu, Ti; Stock, Ann M (2005) A common dimerization interface in bacterial response regulators KdpE and TorR. Protein Sci 14:3077-88 |
