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Originally published In Press as doi:10.1074/jbc.M611593200 on February 16, 2007

J. Biol. Chem., Vol. 282, Issue 17, 12860-12870, April 27, 2007
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PilZ Domain Proteins Bind Cyclic Diguanylate and Regulate Diverse Processes in Vibrio cholerae*

Jason T. Pratt, Rita Tamayo, Anna D. Tischler1, and Andrew Camilli2

From the Howard Hughes Medical Institute and the Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts 02111

Cyclic diguanylate (c-di-GMP) is an allosteric activator and second messenger implicated in the regulation of a variety of biological processes in diverse bacteria. In Vibrio cholerae, c-di-GMP has been shown to inversely regulate biofilm-specific and virulence gene expression, suggesting that c-di-GMP signaling is important for the transition of V. cholerae from the environment to the host. However, the mechanism behind this regulation remains unknown. Recently, it was proposed that the PilZ protein domain represents a c-di-GMP-binding domain. Here we show that V. cholerae PilZ proteins bind c-di-GMP specifically and are involved in the regulation of biofilm formation, motility, and virulence. These findings confirm a role for PilZ proteins as c-di-GMP-sensing proteins within the c-di-GMP signaling network.


Received for publication, December 19, 2006

* This work was supported by National Institutes of Health Grant AI45746 (to A. C.) and Center for Gastroenterology Research on Absorptive and Secretory Processes, New England Medical Center, Grant P30DK34928. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement"in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 Present address: Laboratory of Infection Biology, The Rockefeller University, 1230 York Ave., New York, NY 10021.

2 To whom correspondence should be addressed: Howard Hughes Medical Institute and Dept. of Molecular Biology and Microbiology, Tufts University, 136 Harrison Ave., Boston, MA 02111. Tel.: 617-636-2144; Fax: 617-636-2175; E-mail: andrew.camilli{at}tufts.edu.


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