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Originally published In Press as doi:10.1074/jbc.M212170200 on February 24, 2003

J. Biol. Chem., Vol. 278, Issue 19, 17314-17319, May 9, 2003
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A Developmentally Regulated Two-component Signal Transduction System in Chlamydia*

Ingrid Chou KooDagger and Richard S. StephensDagger §

From the Dagger  Division of Infectious Diseases, School of Public Health, University of California, Berkeley, California 94720-7360 and the § Francis I. Proctor Foundation, University of California, San Francisco, California 94143

Two-component systems allow bacteria to adapt to changing environmental conditions and may induce developmental changes necessary for survival. Chlamydia trachomatis alternates between two distinct developmental forms, each optimized for survival in a separate niche. Transcriptional regulation of development is not understood. The C. trachomatis genome sequence revealed a single pair of genes (ctcB-ctcC) predicted to encode proteins with sequence conservation to bacterial two-component systems. Sequence analysis revealed that the sensor kinase, CtcB, possessed an energy-sensing PAS domain and phosphorylation site. The response regulator, CtcC, had homology to sigma 54 activators, possessing conserved receiver and ATPase domains and phosphorylation site, but lacked the C-terminal DNA-binding domain. ctcB and ctcC were expressed late in the developmental cycle, and both proteins were detected in EB lysates. Recombinant CtcB and CtcC were purified from denatured Escherichia coli inclusion bodies and refolded. CtcC was found to aggregate as dimers and tetramers in solution. In vitro phosphorylation assays showed that CtcB autophosphorylated in the presence of Mg2+, Mn2+, and Fe2+ and transferred the phosphoryl group in the presence of CtcC. Collectively, these results show that CtcB and CtcC function as a two-component system and are likely responsible for transcriptional regulation by sigma 54 holoenzyme during late-stage chlamydial development.


* This work was supported by National Institutes of Health Grant AI42156.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Division of Infectious Diseases, School of Public Health, 140 Warren Hall, Berkeley, CA 94720-7360. E-mail: rss@uclink4.berkeley.edu.


Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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